Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
Quercetin Inhibits Gastric Cancer Progression via FAM198B/MAPK Pathway Modulation.
Deng H, Xiao Q, Xu X … +2 more , Zhang L, Zhang Y
Pharmgenomics Pers Med · 2025 · PMID 40390771 · Full text
BACKGROUND: The family with the sequence similarity 198 member B (FAM198B) has been found to contribute to the progression of gastric cancer (GC). However, the role and molecular mechanism of FAM198B in GC remains poorly...
BACKGROUND: The family with the sequence similarity 198 member B (FAM198B) has been found to contribute to the progression of gastric cancer (GC). However, the role and molecular mechanism of FAM198B in GC remains poorly understood. This work found a link between FAM198B and quercetin, and the regulatory effect of FAM198B on the MAPK pathway of GC. METHODS: FAM198B expression was identified through multiple public data sets and verified in clinical tissue samples. The associations between FAM198B and the prognosis of patients with GC were analyzed via the Kaplan‒Meier plotter and Cox regression analysis. Gene set enrichment analysis, coexpressed genes, and RNA sequencing were used to explore the related functions and signaling pathways of FAM198B in GC. In vitro assays assessed the effects of FAM198B knockdown on GC cells. FAM198B was found as a quercetin target by the HERB database and in vitro assays. RESULTS: FAM198B was highly expressed in tissues from GC patients (<0.001) and was positively associated with poor prognosis (<0.001) and immune cell infiltration in GC patients. FAM198B knockdown inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells (all <0.05). In addition, FAM198B knockdown decreased the phosphorylation of p-Erk1/2 and p-p38 in GC cells (all <0.01). Quercetin inhibited FAM198B expression and the phosphorylation of p-Erk1/2 and p-p38 in GC cells (all <0.05). CONCLUSION: Quercetin inhibits the proliferation, migration, invasion, and EMT of GC cells by inhibiting the FAM198B/MAPK signaling pathway. These discoveries lay the groundwork for developing the treatment of GC by quercetin and targeting FAM198B. In the future, more preclinical and clinical studies are needed to confirm the efficacy and safety of quercetin and target FAM198B in GC.
Prevalence of Variants in Patients with Cardiovascular Disease from the Yunnan-Guizhou Plateau in Southwestern China.
Li XP, Wang JL, Lei SX … +11 more , Chen BY, Ma X, He F, Yue CF, Liu HX, Hu JP, Xiong Q, Ji T, Zhang ZF, Sun Y, Li HW
Pharmgenomics Pers Med · 2025 · PMID 40330492 · Full text
BACKGROUND AND PURPOSE: The CYP2C19 enzyme is essential for activation of the antiplatelet drug clopidogrel. Genetic variations in CYP2C19 are known to influence individual drug responses. Here, differences in alleles,...
BACKGROUND AND PURPOSE: The CYP2C19 enzyme is essential for activation of the antiplatelet drug clopidogrel. Genetic variations in CYP2C19 are known to influence individual drug responses. Here, differences in alleles, genotypes, and phenotypes in patients with cardiovascular disease from the Yunnan-Guizhou Plateau were systematically surveyed to provide a reference for appropriate treatment approaches. METHODS: The , and variants were determined by RT-qPCR in 1934 patients with cardiovascular disease from 10 different areas of the Yunnan-Guizhou Plateau. Clinical data were analyzed using χ tests. RESULTS: The proportions of the , and alleles in the study cohort were 64.94, 29.81, 4.42, and 0.83%, respectively, while the frequencies of nine observed genotypes () were 1.03, 42.09, 0.57, 0.05, 38.73, 5.95, 8.89, 2.53, and 0.16%, respectively. Four metabolic phenotypes were found in the population, namely, rapid (1.03%), normal (42.09%), intermediate (45.29%), and poor (11.58%) metabolizers. Regional differences in allele and phenotype distribution were observed. CONCLUSION: These results represent the first comprehensive profile of variants in patients with cardiovascular disease from the Yunnan-Guizhou Plateau, offering a valuable genetic reference for the selection of optimal treatment strategies.
Clinicopathological and Molecular Features of Primary Inflammatory Myofibroblastic Tumor in Nasal Cavity and Paranasal Sinuses.
Zhao Y, Ma D, Wan H … +1 more , Piao Y
Pharmgenomics Pers Med · 2025 · PMID 40321626 · Full text
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) in the nasal cavity and sinuses is rare and has special clinical and pathological characteristics with poor prognosis. This study aimed to investigate the clinicopatho...
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) in the nasal cavity and sinuses is rare and has special clinical and pathological characteristics with poor prognosis. This study aimed to investigate the clinicopathological and molecular features of primary IMT in the nasal cavity and paranasal sinuses. METHODS: The clinical features, histopathological findings, immunohistochemical findings and results of molecular genetic examination were retrospectively analyzed in 25 patients who were diagnosed with IMT in the nasal cavity and paranasal sinuses. RESULTS: Tumor tissues were mainly composed of obese spindle-shaped myofibroblasts, fibroblasts, and chronic inflammatory cells. The inflammatory cells included plasma cells, lymphocytes, eosinophils, foam histiocytes and multinuclear giant cells. Immunohistochemical staining showed the tumor was positive to anaplastic lymphoma kinase (ALK) in two patients. fusion mutation was detected by PCR in only 1 patient. CONCLUSION: Nasal and paranasal sinus IMTs are rare, exhibit histopathological diversity with low specificity, and require careful differentiation from inflammatory and autoimmune disorders. These tumors demonstrate a worse prognosis compared to IMTs in other anatomic locations, along with a significantly lower rate of ALK gene rearrangement. Identifying molecular target alterations can enhance precision diagnosis and targeted therapeutic strategies.
Novel Frameshift Mutation as a Cause of Allan-Herndon-Dudley Syndrome and its Implications for Carrier Screening.
Lin P, Liu H, Lou J … +7 more , Lyu G, Li Y, He P, Fu Y, Zhang R, Zhang Y, Yan T
Pharmgenomics Pers Med · 2025 · PMID 40291819 · Full text
BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder caused by mutations in the solute carrier family 16-member 2 () gene. This syndrome leads to significant psychomotor disabil...
BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked neurodevelopmental disorder caused by mutations in the solute carrier family 16-member 2 () gene. This syndrome leads to significant psychomotor disabilities, thyroid dysfunction, and abnormal brain development. This case report describes the genetic cause of AHDS in a male proband and to expanding the mutation spectrum of the gene. METHODS: A blood specimen was collected from a one-year-old child with delayed development and abnormal thyroid function and this was followed by whole-exome sequencing (WES) was performed on the proband to identify potential genetic mutations. Sanger sequencing was subsequently used to confirm the findings and determine the inheritance pattern of the mutation within the family. RESULTS: The proband, who presented with developmental delay, thyroid dysfunction, and abnormal brain development, was found to have a novel hemizygous frameshift mutation, c.513_538del (p.Ile172Cysfs*60), in the gene (NM_006517.5). This mutation was inherited from his asymptomatic mother, confirming the X-linked inheritance pattern. The mutation is classified as likely pathogenic, contributing to the clinical presentation observed in the proband. CONCLUSION: This study identified a novel frameshift mutation in the gene associated with AHDS, thereby expanding the known mutation spectrum of this gene. Given the significant impact of AHDS on neural development and hormone secretion, it is recommended that this gene be included in carrier screening panels in China, particularly for families with a history of related neurodevelopmental disorders.
Association of MiRNA Polymorphisms Involved in the PI3K/ATK/GSK3β Pathway with T2DM in a Chinese Population.
Zhou X, Yang M, Yang Y … +5 more , Xu F, Wang F, Jiao M, Tao W, Li Y
Pharmgenomics Pers Med · 2025 · PMID 39974346 · Full text
BACKGROUND: Single nucleotide polymorphisms (SNPs) in miRNA genes can influence the expression of miRNAs that modulate the PI3K/AKT/GSK3β pathway and play crucial roles in type 2 diabetes mellitus (T2DM) susceptibility....
BACKGROUND: Single nucleotide polymorphisms (SNPs) in miRNA genes can influence the expression of miRNAs that modulate the PI3K/AKT/GSK3β pathway and play crucial roles in type 2 diabetes mellitus (T2DM) susceptibility. The purpose of this study was to investigate the association of SNPs in miRNA genes targeting the PI3K/AKT/GSK3β pathway with T2DM. METHODS: This case-control study included 1,416 subjects with T2DM and 1,694 non-diabetics. Eleven SNPs in miRNA genes (rs895819 in miR-27a, rs11888095 in miR-128a, rs2292832 in miR-149, rs6502892 in miR-22, rs13283671 in miR-31, rs1076063 and rs1076064 in miR-378a, rs10061133 in miR-449b, rs3746444 in miR-499a and rs678956 and rs476364 in miR-326) involved in PI3K/AKT/GSK3β pathway were genotyped by TaqMan Genotyping Assay, and the associations of these SNPs with T2DM were analyzed using online SHesis and SNPstats. RESULTS: The results showed that miR-378a rs1076064 G allele could be a protective factor against T2DM (p<0.001, OR=0.828; 95% CI:0.749-0.916), whereas the miR-31 rs13283671 C allele could increase the risk of developing T2DM (p=0.003, OR=1.193; 95% CI:1.060-1.342). In addition, the miR-378a rs1076063A-rs1076064G haplotype could be a protective against T2DM (p<0.001, OR=0.731; 95% CI:0.649-0.824). According to inheritance mode analysis, compared with the AA-AG genotype, the GG genotype of rs1076064 showed a protective effect in T2DM in the recessive mode (p<0.01, OR=0.71; 95% CI: 0.59-0.84). For rs13283671, compared with the TT genotype, the CT-CC genotype showed a risk effect in T2DM in the dominant inheritance model (p<0.01, OR=1.29; 95% CI: 1.12-1.49). Genotype-Tissue Expression (GTEx) Portal database analysis showed that miR-31 rs13283671 CT and CC genotypes had lower AKT expression than TT genotypes. CONCLUSION: In conclusion, rs13283671 in miR-31 and rs1076064 in miR-378a involved in the PI3K/AKT/GSK3β pathway were associated with T2DM susceptibility in a Chinese population.
Pharmacogenomics of Chemotherapies for Childhood Cancers in Africa: A Scoping Review.
Katabalo DM, Mwita S, Liwa AC … +2 more , Kidenya BR, Schroeder K
Pharmgenomics Pers Med · 2025 · PMID 39968370 · Full text
BACKGROUND: Pharmacogenomics holds significant promise in improving the efficacy and safety of chemotherapy for childhood cancers. However, the field remains underexplored in Africa, where high genetic diversity and subs...
BACKGROUND: Pharmacogenomics holds significant promise in improving the efficacy and safety of chemotherapy for childhood cancers. However, the field remains underexplored in Africa, where high genetic diversity and substantial disease burdens, including cancers, create unique challenges. This review investigates the current state of pharmacogenomics research in childhood cancer chemotherapies across Africa, focusing on genetic variations influencing chemotherapy efficacy and adverse drug reactions. It also highlights critical gaps, such as limited infrastructure and insufficient healthcare worker knowledge, and emphasizes the importance of capacity-building initiatives in the region. METHODS: A scoping review was conducted encompassing studies published up to September 2024 that examined pharmacogenomic variations associated with chemotherapies in childhood cancer patients across Africa. The review included laboratory genetic analyses and surveys assessing healthcare workers' knowledge, attitudes, and perceptions regarding pharmacogenomics, particularly in the context of pediatric oncology. RESULTS: A total of 12 genes were identified across eight studies, including . The most studied genes were and , which are involved in the metabolism of 6-mercaptopurine (6-MP) and vincristine, respectively. These studies spanned five African countries, including Kenya, Egypt, Zimbabwe, Nigeria, Tunisia, and Libya, and focused primarily on childhood cancers, particularly acute lymphoblastic leukemia. Chemotherapies frequently studied were 6-MP (reported in five studies), vincristine, cyclophosphamide, and methotrexate. Knowledge of pharmacogenomics among healthcare workers in Africa remains low, though a positive attitude towards its clinical applications was observed. CONCLUSION: Pharmacogenomic variants, such as TPMT*3A, 3C, and CYP3A53, *6, significantly impact drug metabolism in African children with cancer. However, research remains regionally limited, and gaps in infrastructure and healthcare worker training persist. Expanding research efforts and improving pharmacogenomics capacity through pharmacist training and capacity-building initiatives are essential to advancing personalized medicine in Africa, ultimately improving treatment outcomes for pediatric cancer patients.
A Novel Pathogenic Splicing Mutation of is Responsible for a Boy with Joubert Syndrome Exhibiting Orofaciodigital Spectrum Anomalies, Polydactyly and Retinitis Pigmentosa.
Chen L, Zhao MF, Deng HW … +7 more , Liao M, Fan LL, Zhong QB, Wang J, Li K, Wu ZH, Yin JY
Pharmgenomics Pers Med · 2025 · PMID 39925483 · Full text
Joubert syndrome (JS) is an infrequent congenital neurodevelopmental ciliopathy, typically identified in children around the average age of 33 months. This disorder is characterized by developmental delay, cognitive impa...
Joubert syndrome (JS) is an infrequent congenital neurodevelopmental ciliopathy, typically identified in children around the average age of 33 months. This disorder is characterized by developmental delay, cognitive impairment, and infantile hypotonia that may evolve into ataxia. Mutations in results in Joubert syndrome with a variety of phenotypes. Here, we identified a child who presented with Joubert syndrome exhibiting orofaciodigital spectrum anomalies, polydactyly, and retinitis pigmentosa. Whole exome sequencing and Sanger sequencing revealed a splicing mutation (NM_003611.2, c.2387+1G>A) in the gene of the patient and his mother. mRNA sequencing further confirmed this mutation. However, since the patient is homozygous and the mother is heterozygous, only the patient has the phenotype and the mother is normal. This mutation can lead to the loss of sixth coiled-coil domains of OFD1 protein, which further disrupt the ciliary signaling pathway and Hedgehog signaling pathway. This study presents a new case of JS and expands the mutant spectrum of , but also enhances our understanding of the mechanism by which is associated with ciliosis.
Naoxintong Is Involved in the Coagulation Regulation of Warfarin Through the MAPK Pathway.
Luo X, Chen L, Xu J … +1 more , Li J
Pharmgenomics Pers Med · 2025 · PMID 39906888 · Full text
OBJECTIVE: To explore the effect of Naoxintong (NXT) on warfarin anticoagulation therapy and its potential mechanism. METHODS: TCSMP, SwissTargetprediction, SuperPred, SEA, and Batmanic-TCM were used to search for active...
OBJECTIVE: To explore the effect of Naoxintong (NXT) on warfarin anticoagulation therapy and its potential mechanism. METHODS: TCSMP, SwissTargetprediction, SuperPred, SEA, and Batmanic-TCM were used to search for active ingredients and targets of NXT and warfarin; the DisGENT database was used to find disease targets of coagulation disorders. Cytoscape software was applied to construct the "drug-target"network; the protein interaction network (PPI) was used to study the protein-protein interaction. GO and KEGG were used for functional analysis. The effect of NXT on warfarin anticoagulation was then tested in rats by analyzing coagulation factors in blood before and after drug administration. The expression of MAPK in the liver tissue was determined by Western blot. RESULTS: The top five components of NXT affecting warfarin anticoagulation degree value were MOL000098, MOL000422, MOL000006, MOL000358, and MOL000449. TP53, AKT1, SRC, TNF, HSP90AA1, STAT3, JUN, IL6, EGFR, and ESR1 were the core targets of NXT, while MAPK9, MAP3K5, MAPK8, and MAPK1 in the MAPK family were important targets of NXT in the coagulation process. In vivo testing indicated that NXT may be able to participate in the regulation of the warfarin coagulation process through multiple targets and multiple pathways, which may be related to MAPK. CONCLUSION: Our data suggests that NXT is involved in the coagulation regulation of warfarin through the MAPK pathway.
Pharmacogenomics Tools for Precision Public Health and Lessons for Low- and Middle-Income Countries: A Scoping Review.
Borbón A, Briceño JC, Valderrama-Aguirre A
Pharmgenomics Pers Med · 2025 · PMID 39902237 · Full text
Pharmacogenomics is the integration of genomics and pharmacology to optimize drug response and reduce side effects. In terms of personalized or individualized medicine, PGx is defined as the identification and analysis o...
Pharmacogenomics is the integration of genomics and pharmacology to optimize drug response and reduce side effects. In terms of personalized or individualized medicine, PGx is defined as the identification and analysis of specific genetic variants associated with particular drug treatments for each patient. Under a precision public health (PPH) approach, population-level data are analyzed to generate public health strategies. The objective of this study was to conduct a scoping review of technological tools, examining their evolution, the predominance of high-income countries in their development, and the gaps and needs for genomic data and advances in low- and middle-income countries (LMICs). This review was conducted in accordance with the ScPRISMA guidelines. A search was conducted in PubMed, Web of Science and Embase until January 2024. A total of 40 documents were selected, which revealed the continuous evolution and progressive development of pharmacogenomic tools. The technological tools developed come from high-income countries, particularly the United States, Canada, China, and several European nations, where international collaboration has been essential to maintain and expand these tools, which have evolved to keep pace with the rapid generation of genomic data. This trend shows a scarce development of technological tools for public health precision in LMICs, which evidences the need to increase investment in genomic research infrastructure in this aspect and in the development of capacities to guarantee global accessibility and boost PPH for all populations.
Identification of Bacterial Lipopolysaccharide-Associated Genes and Molecular Subtypes in Autism Spectrum Disorder.
He Y, He Y, Cheng B
Pharmgenomics Pers Med · 2025 · PMID 39850061 · Full text
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by diverse symptoms affecting social interaction, communication, and behavior. This research aims to explore bacterial lipopolys...
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by diverse symptoms affecting social interaction, communication, and behavior. This research aims to explore bacterial lipopolysaccharide (LPS)- and immune-related (BLI) molecular subgroups in ASD to enhance understanding of the disorder. METHODS: We analyzed 89 control samples and 157 ASD samples from the GEO database, identifying BLI signatures using least absolute shrinkage and selection operator regression (LASSO) and logistic regression machine learning algorithms. A nomogram prediction model was developed based on these signatures, and we performed Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and immune cell infiltration analysis to assess the impact of BLI subtypes and their underlying mechanisms. RESULTS: Our findings revealed 17 differentially expressed BLI genes in children with ASD, with BLNK, MAPK8, PRKCQ, and TNFSF12 identified as potential biomarkers. The nomogram demonstrated high diagnostic accuracy for ASD. We delineated two distinct molecular subtypes (Cluster 1 and Cluster 2), with GSVA indicating that Cluster 2 showed upregulation of immune- and inflammation-related pathways. This cluster exhibited increased levels of antimicrobial agents, chemokines, cytokines, and TNF family cytokines, alongside activation of bacterial lipoprotein-related pathways. A significant correlation was found between these pathways and distinct immune cell subtypes, suggesting a potential mechanism for neuroinflammation and immune cell infiltration in ASD. CONCLUSION: Our research highlights the role of BLI-associated genes in the immune responses of individuals with ASD, indicating their contribution to the disorder's typification. The interplay between bacterial components, genetic predisposition, and immune dysregulation offers new insights for understanding ASD and developing personalized interventions.
The Association of PLA2G7 Gene Polymorphisms with Serum Lp-PLA2 Activity and Lipid Profile in Han Chinese Patients with Coronary Heart Disease.
Wang Y, Shi Y, Wu Z … +8 more , Gao J, Wang J, Li L, Wan Y, Lang A M, Zhang J, Wang H, Hou Y
Pharmgenomics Pers Med · 2024 · PMID 39723113 · Full text
PURPOSE: This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipas...
PURPOSE: This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles. METHODS: A total of 93 han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing. Concurrently, multiple lipid parameters were measured and analyzed. RESULTS: Among these Han Chinese CHD patients, the PLA2G7 gene rs1051931 (c.1136T>C p.Val379Ala) rare variant was highly prevalent (variant rate: 94.62%) among the study population, and showed negative correlation with serum Lp-PLA2 activity. The rs1765208290 (c.233G>A p.Gly78Asp) rare variant showed positive correlation with TG, ApoA, ApoB, HDL, LDL and TCHO levels in the serum. Strong linkage disequilibrium was observed between the rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe), both of which were related to lower Lp-PLA2 activity. CONCLUSION: In these Han Chinese CHD patients, the rs1051931 (c.1136T>C p.Val379Ala) rare variant in the PLA2G7 gene is closely linked to decreased Lp-PLA2 activity, whereas the rs1765208290 (c.233G>A p.Gly78Asp) rare variant influences lipid homeostasis. The strong LD between rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe) loci may act synergistically to reduce Lp-PLA2 activity.
The Genetic and Molecular Drivers of Multiple Myeloma: Current Insights, Clinical Implications, and the Path Forward.
Ram M, Fraser MR, Vieira Dos Santos J … +5 more , Tasakis R, Islam A, Abo-Donia JU, Parekh S, Lagana A
Pharmgenomics Pers Med · 2024 · PMID 39723112 · Full text
BACKGROUND: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The disease's complexity is underpinned by a variety of genetic...
BACKGROUND: Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The disease's complexity is underpinned by a variety of genetic and molecular abnormalities that drive its progression. METHODS: This review was conducted through a state-of-The-art literature search, primarily utilizing PubMed to gather peer-reviewed articles. We focused on the most comprehensive and cited studies to ensure a thorough understanding of the genetic and molecular landscapes of MM. RESULTS: We detail primary and secondary alterations such as translocations, hyperdiploidy, single nucleotide variants (SNVs), copy number alterations (CNAs), gene fusions, epigenetic modifications, non-coding RNAs, germline predisposing variants, and the influence of the tumor microenvironment (TME). Our analysis highlights the heterogeneity of MM and the challenges it poses in treatment and prognosis, emphasizing the distinction between driver mutations, which actively contribute to oncogenesis, and passenger mutations, which arise due to genomic instability and do not contribute to disease progression. CONCLUSION & FUTURE PERSPECTIVES: We report key controversies and challenges in defining the genetic drivers of MM, and examine their implications for future therapeutic strategies. We discuss the importance of systems biology approaches in understanding the dependencies and interactions among these alterations, particularly highlighting the impact of double and triple-hit scenarios on disease outcomes. By advancing our understanding of the molecular drivers and their interactions, this review sets the stage for novel therapeutic targets and strategies, ultimately aiming to improve clinical outcomes in MM patients.
PEAR1, PON1, CYP2C19, CYP1A2 and F2R Polymorphisms are Associated with MACE in Clopidogrel-Treated Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.
Du P, Li X, Li D … +6 more , Ma Y, Ni M, Li Y, Li W, Wang A, Xu X
Pharmgenomics Pers Med · 2024 · PMID 39723111 · Full text
OBJECTIVE: The objective of this study was to evaluate the impact of clopidogrel-related gene polymorphisms on the occurrence of recurrent thrombotic events and cardiovascular death in patients with acute coronary syndro...
OBJECTIVE: The objective of this study was to evaluate the impact of clopidogrel-related gene polymorphisms on the occurrence of recurrent thrombotic events and cardiovascular death in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). METHODS: We conducted genotype testing for 26 specific loci mapped to 18 clopidogrel-associated genes in ACS patients who had undergone PCI and were receiving dual antiplatelet therapy only involving clopidogrel. We documented major adverse cardiovascular events (MACE) and clinical endpoints, analyzing the effect of genetic polymorphisms on treatment outcomes. RESULTS: A total of 200 patients were enrolled in the study, with ischemic events occurring in 21 cases. Carriers of the T-allele for rs41273215 (), rs662 (), and the A-allele for rs4244285 (), as well as the C-allele for rs762551 (), exhibited a significant increase in the risk of MACE (OR = 2.76, 95% CI = 1.46-5.22, P = 0.002; OR = 3.72, 95% CI = 1.82-7.64, P = 0.0003; OR = 3.86, 95% CI = 1.89-7.86, P = 0.0002; OR = 2.40, 95% CI = 1.27-4.55, P = 0.007). Notably, the variant T-allele of rs168753 () was associated with a significant reduction in the risk of such events (OR = 0.29, 95% CI = 0.12-0.67, P = 0.004). No significant associations were found between other single nucleotide polymorphisms (SNPs) and clinical endpoints. CONCLUSION: Polymorphisms in rs41273215 (), rs662 (), rs4244285 (), and rs762551 () were correlated with an increased risk of MACE in PCI patients. Conversely, the rs168753 () polymorphism was linked to improved cardiovascular outcomes. Genotyping for these polymorphisms could be instrumental in identifying patients at heightened risk for MACE.
Associations Between the Polymorphisms in the Coding Sequence of SLCO1B1 and Blood Lipid Levels Before and After Treatment by Atorvastatin in the Chinese Han Adults with Dyslipidemia.
Chen C, Tian Y, Jia F … +7 more , Feng M, Zhang G, Li Q, Zhang Y, Sun N, Hu S, Ji Z
Pharmgenomics Pers Med · 2024 · PMID 39720770 · Full text
PURPOSE: Atorvastatin is commonly used to treat dyslipidemia; however, individual responses vary considerably. This study endeavors to evaluate the relationship between polymorphisms in the coding sequence (CDS) of SLCO1...
PURPOSE: Atorvastatin is commonly used to treat dyslipidemia; however, individual responses vary considerably. This study endeavors to evaluate the relationship between polymorphisms in the coding sequence (CDS) of SLCO1B1 gene and blood lipid levels before and after atorvastatin treatment among the Chinese Han adults with dyslipidemia. PATIENTS AND METHODS: A total of 165 Chinese Han adults undergoing atorvastatin therapy were enrolled in this study and followed up quarterly. The complete CDS of the SLCO1B1 gene was sequenced to detect polymorphisms. Statistical analysis was utilized to assess the impacts of sex, age, body mass index (BMI), and polymorphisms on blood lipid levels before and after atorvastatin treatment. RESULTS: Fourteen polymorphisms were identified in the SLCO1B1 CDS. Among them, four polymorphisms had mutant alleles present in over 20 patients. No polymorphism was found to correlate with blood lipid levels before treatment; in contrast, age, sex, and BMI did show correlations (<0.05). Notably, females had higher baseline blood lipid levels than males, indicating that sex had a more significant impact on baseline levels than age and BMI. The polymorphism rs2306283 was significantly correlated with the efficacy of atorvastatin (<0.05), whereas age, sex, and BMI were not. Carriers of the rs2306283 AA allele experienced a substantially greater reduction in total cholesterol (TC) and triglyceride (TG) levels after atorvastatin treatment. The other polymorphisms did not demonstrate any significant impact on atorvastatin's efficacy. CONCLUSION: This study delved into the intricate genetic structure of polymorphisms in SLCO1B1 CDS and their roles in lipid metabolism and atorvastatin's efficacy among Chinese Han adults with dyslipidemia. The findings underscore the crucial role of the rs2306283 polymorphism in the response to atorvastatin's efficacy, highlighting the significance of pharmacogenomics in personalized medicine. It is thus advisable to consider genetic testing for SLCO1B1 variants to optimize atorvastatin therapy.
CD27 as a Diagnostic Biomarker and Its Role in Immune Heterogeneity and Predicting Clinical Drug Responses in Hashimoto's Thyroiditis.
Dong YM, Bao GQ
Pharmgenomics Pers Med · 2024 · PMID 39717528 · Full text
OBJECTIVE: To identify key genes and potential molecular mechanisms associated with Hashimoto's thyroiditis (HT) to provide new insights for the development of diagnostic and therapeutic targets for this disease. METHODS...
OBJECTIVE: To identify key genes and potential molecular mechanisms associated with Hashimoto's thyroiditis (HT) to provide new insights for the development of diagnostic and therapeutic targets for this disease. METHODS: Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify the differentially expressed genes (DEGs) associated with HT. A protein-protein interaction (PPI) network was used to obtain hub genes, with CD27 emerging as the key gene in HT. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, Gene Set Enrichment Analysis (GSEA), and HT-infiltrating immune cell components as well as functions were performed to further investigate the role and potential mechanism of CD27 in cohorts with high and low expression of CD27. RESULTS: CD27 was found to be upregulated in HT tissues and showed considerable clinical utility in HT. The CD27 of the high-expression cohort exhibited a higher enrichment in immune-related biological processes than the low-expression group. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis revealed that several activated HT-infiltrating immune cells were strongly associated with CD27, suggesting that CD27 has the potential to be a marker for the immune state in HT. CONCLUSION: In our study, CD27 was found to contribute to predicting clinical outcomes in patients with HT, including disease status and response to immunotherapy. CD27 is a promising biomarker for HT microenvironment remodeling, offering insights into new therapeutic approaches to improve treatment of HT.
Prognostic Value and Immunological Role of POP7 in Clear Cell Renal Cell Carcinoma.
Lou N, Meng X, Yu T … +5 more , Li W, Lv X, Han W, Xiao W, Shi Y
Pharmgenomics Pers Med · 2024 · PMID 39620194 · Full text
BACKGROUND: Studies have found that RNA-binding proteins (RBPs) are participated in the occurrence or development of tumours. However, the role of processing of precursor family (POP family) in clear cell renal cell carc...
BACKGROUND: Studies have found that RNA-binding proteins (RBPs) are participated in the occurrence or development of tumours. However, the role of processing of precursor family (POP family) in clear cell renal cell carcinoma (ccRCC) has not been studied yet. Here, we analyzed the expression and prognostic value of POP family in ccRCC analyzed and subsequently revealed the relationship between POP7 and immune infiltration in ccRCC patients. METHODS: POP family expression in cancer and normal tissues was analyzed in Cancer Genome Atlas pan-cancer (TCGA-pan-cancer). Kaplan-Meier (KM) survival analysis, univariable and multivariable analysis demonstrated the survival of ccRCC with POP family in Kidney Clear Cell Carcinoma (TCGA-KIRC). POP7 mRNA and protein expression were verified by Gene Expression Omnibus (GEO) data, the quantitative real-time polymerase chain reaction (qRT-PCR), and Office of Cancer Clinical Proteomics Research (CPTAC). The diagnostic ability of POP7 mRNA and protein expression was achieved with ROC curves. Gene Set Enrichment Analysis (GSEA) and TiMER2 evaluated pathogenesis role and immune infiltration of POP7in ccRCC. RESULTS: There is a significant difference in expression of POP family in TCGA-pan-cancer, especially in ccRCC. KM survival analysis, univariable and multivariable analysis demonstrated low expression of POP7 and was associated with poor OS and poor DFS. GEO data, the qRT-PCR, and CPTAC verified the high expression of POP7 mRNA and protein in ccRCC. ROC curves verified a valuable diagnostic ability of POP7 in mRNA and protein expression. GSEA demonstrated POP7 was associated with CD8+cells, CD4+cells, natural killer (NK) cells, and helper T (TH1) cells. TiMER2 results indicated POP7 had a positive correlation with T cell regulatory (Tregs) and myeloid-derived suppressor cells (MDSC) in ccRCC and was an immunosuppressor for ccRCC. CONCLUSION: POP7 was a reliable immunosuppressor, predictor and biomarker for ccRCC.
Immune Microenvironment Alterations and Identification of Key Diagnostic Biomarkers in Chronic Kidney Disease Using Integrated Bioinformatics and Machine Learning.
Shi J, Xu A, Huang L … +3 more , Liu S, Wu B, Zhang Z
Pharmgenomics Pers Med · 2024 · PMID 39588536 · Full text
BACKGROUND: Chronic kidney disease (CKD) involves complex immune dysregulation and altered gene expression profiles. This study investigates immune cell infiltration, differential gene expression, and pathway enrichment...
BACKGROUND: Chronic kidney disease (CKD) involves complex immune dysregulation and altered gene expression profiles. This study investigates immune cell infiltration, differential gene expression, and pathway enrichment in CKD patients to identify key diagnostic biomarkers through machine learning methods. METHODS: We assessed immune cell infiltration and immune microenvironment scores using the xCell algorithm. Differentially expressed genes (DEGs) were identified using the limma package. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to evaluate pathway enrichment. Machine learning techniques (LASSO and Random Forest) pinpointed diagnostic genes. A nomogram model was constructed and validated for diagnostic prediction. Spearman correlation explored associations between key genes and immune cell recruitment. RESULTS: The CKD group exhibited significantly altered immune cell infiltration and increased immune microenvironment scores compared to the normal group. We identified 2335 DEGs, including 124 differentially expressed immune-related genes. GSEA highlighted significant enrichment of inflammatory and immune pathways in the high immune score (HIS) subgroup, while GSVA indicated upregulation of immune responses and metabolic processes in HIS. Machine learning identified four key diagnostic genes: RGS1, IL4I1, NR4A3, and SOCS3. Validation in an independent dataset (GSE96804) and clinical samples confirmed their diagnostic potential. The nomogram model integrating these genes demonstrated high predictive accuracy. Spearman correlation revealed positive associations between the key genes and various immune cells, indicating their roles in immune modulation and CKD pathogenesis. CONCLUSION: This study provides a comprehensive analysis of immune alterations and gene expression profiles in CKD. The identified diagnostic genes and the constructed nomogram model offer potent tools for CKD diagnosis. The immunomodulatory roles of RGS1, IL4I1, NR4A3, and SOCS3 warrant further investigation as potential therapeutic targets in CKD.
Hsa_circ_0078767 Enhances Osteosarcoma Chemoresistance to Doxorubicin Through the Regulation of the miR-188-3p/GPX4 Axis.
Tang Y, He Y, Wu L
Pharmgenomics Pers Med · 2024 · PMID 39588535 · Full text
BACKGROUND: Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a medi...
BACKGROUND: Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS. METHODS: Levels of hsa_circ_0078767, miR-188-3p, and glutathione peroxidase 4 (GPX4) in OS clinical tissue samples and cell lines were evaluated by quantitative polymerase chain reaction (qPCR) and Western blotting. Associations between hsa_circ_0078767 levels in clinical samples and patient overall survival were assessed with Kaplan-Meier curves. CCK-8 assays were utilized as a means of examining DOX half-inhibitory concentration (IC) values. RNA immunoprecipitation and pull-down, as well as reporter assays, investigated interactions between hsa_circ_0078767, miR-188-3p, and GPX4 within OS cells exhibiting DOX resistance. RESULTS: OS patient tissues and cell lines resistant to DOX exhibited elevated hsa_circ_0078767 and GPX4 expression together with a reduction in miR-188-3p levels. Inhibiting hsa_circ_0078767 expression contributed to a profound decrease in the ability of OS tumors to resist DOX. Mechanistically, it was determined that hsa_circ_0078767 can enhance DOX chemoresistance through its ability to bind and sequester miR-188-3p, which otherwise negatively modulates GPX4 to enhance chemosensitivity. Accordingly, the sequestration of miR-188-3p by hsa_circ_0078767 led to the derepression and upregulation of GPX4. CONCLUSION: Hsa_circ_0078767 was found to modulate miR-188-3p/GPX4 signaling to enhance OS cell resistance to DOX treatment and facilitate disease progression. As such, hsa_circ_0078767 may represent a valuable biomarker or target for use in the context of OS patient management.
Genetic Diversity Landscape in African Population: A Review of Implications for Personalized and Precision Medicine.
Sibomana O
Pharmgenomics Pers Med · 2024 · PMID 39555236 · Full text
INTRODUCTION: Africa, a continent considered to be the cradle of human beings has the largest genetic diversity among its population than other continents. This review discusses the implications of this high African gene...
INTRODUCTION: Africa, a continent considered to be the cradle of human beings has the largest genetic diversity among its population than other continents. This review discusses the implications of this high African genetic diversity to the development of personalized and precision medicine. METHODOLOGY: A comprehensive search across PubMed, Google Scholar, Science Direct, DOAJ, AJOL, and the Cochrane Library electronic databases and manual Google searches was conducted using key terms "genetics", "genetic diversity", "Africa", "precision medicine", and "personalized medicine". Updated original and review studies focusing on the implications of African high genetic diversity on personalized and precision medicine were included. Included studies were thematically synthesized to elucidate their positive or negative implications for personalized healthcare, aiming to foster informed clinical practice and scientific inquiry. RESULTS: African populations' high genetic diversity presents opportunities for personalized and precision medicine including improving pharmacogenomics, understanding gene interactions, discovering new variants, mapping disease genes, creating updated genomic reference panels, and validating biomarkers. However, challenges include underrepresentation in studies, scarcity of reference genomes, inaccuracy of genetic testing and interpretation, and ancestry misclassification. Addressing these requires the establishment of genomic research centers, increasing funding, creating biobanks and repositories, education, infrastructure, and international cooperation to enhance healthcare equity and outcomes through personalized and precision medicine. CONCLUSION: High African genetic diversity presents both positive and negative implications for personalized and precision medicine. Deep further research is recommended to harness the challenges and use the opportunities to develop customized treatments.
Pharmacogenomic Study of Selected Genes Affecting Amlodipine Blood Pressure Response in Patients with Hypertension.
Jan A, Alanzi AR, Mothana RA … +6 more , Kaimori JY, Ali SS, Muhammad T, Saeed M, Akbar R, Khan M
Pharmgenomics Pers Med · 2024 · PMID 39492848 · Full text
INTRODUCTION: Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes...
INTRODUCTION: Despite the availability of various antihypertensive medications, the response to these medications varies among individuals. Understanding how individual genetic variations affect drugs treatment outcomes is a key area of focus in precision medicine. This study investigated the correlation between single nucleotide polymorphisms (SNPs) in selected genes (CACNA1C, CACNA1D, ABCB1, ACE, ADBR2, and NOS1AP) and the blood pressure (BP) control by amlodipine. METHODS: Four hundred individuals of Pashtun ethnicity undergoing amlodipine treatment for hypertension were included in the present study and divided into the controlled (BP less than 140/90 mmHg) and uncontrolled (BP greater than 140/90 mmHg) hypertension groups. Blood samples (3 mL) were collected from each participant, and DNA was extracted using the Kit method. Ten SNPs in amlodipine pharmacogenes were selected and genotyped using real-time PCR with the TaqMan system. Logistic regression model was used to determine the association between SNPs and the amlodipine BP response. RESULTS: Notable association were observed between SNP rs2239050/CACNA1C and amlodipine blood pressure response, with GG genotype carriers demonstrating a better response (P=0.004) than individuals carrying CC or CG genotypes. SNP rs312481/CACNA1D also exhibited a positive pharmacogenetic association, Individuals with the GG genotype showing a considerable reduction in BP (P=0.021) compared to participants with AA or GA genotypes. In case of SNP rs429/ACE individuals carrying TA genotype were less likely to achieve BP control (P=0.002) than AA genotype carriers. CONCLUSION: Our finding suggests that the SNPs rs2239050/CACNA1C, rs312481/CACNA1D and rs429/ACE influence amlodipine blood pressure response in patients with hypertension. It is recommended that prior knowledge of amlodipine associated pharmacogenetic variants is important that could improve its treatment outcomes in hypertensive patients.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe