Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
Genetic Polymorphism of NQO1 Influences Susceptibility to Coronary Heart Disease in a Chinese Population: A Cross-Sectional Study and Meta-Anaylsis.
Zhou YY, Sun JH, Wang L … +1 more , Cheng YY
Pharmgenomics Pers Med · 2023 · PMID 37720192 · Full text
OBJECTIVE: The present study is to explore the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. METHODS: This research were selected 80 CHD patients as the observation group and 130 healt...
OBJECTIVE: The present study is to explore the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. METHODS: This research were selected 80 CHD patients as the observation group and 130 healthy people who participated in normal physical examination during the same period as the control group. NQO1 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In addition, we conducted a meta-analysis to summarize the results of three relevant previously published adult population studies on the association between NQO1 gene polymorphism and coronary heart disease (CHD) risk. RESULTS: There were three genotypes (CC, CT, and TT) for NQO1 C609T polymorphism. The significant associations were found in TT genotype and T allele (all <0.05). Specifically, People with the TT genotype have 2.06 times CHD risk as those with the CC genotype. And People with the T allele have 1.62 times CHD risk as those with the C allele. No significant association was found by any genetic models in the meta-analysis (all >0.05). CONCLUSION: NQO1 gene polymorphism increased the CHD risk in a Chinese population. Combined with individual gene polymorphism, the accuracy of risk assessment for CHD can be improved and individualized health education can be provided for CHD patients by nurses.
A Case Report of Cardiofaciocutaneous Syndrome with Pathogenic Variant.
Tang Q, Gong D, Ye XM … +5 more , Xu JR, Yang YC, Yan LJ, Zou L, Wen XL
Pharmgenomics Pers Med · 2023 · PMID 37705935 · Full text
Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous synd...
Craniofacial dysmorphism, cardiac abnormalities, ectodermal abnormalities, psychomotor delay, intellectual disability, and short stature are all hallmarks of the extremely rare disorder known as cardiofaciocutaneous syndrome (CFCS). Although CFCS is considered rare, approximately 300 cases have been documented in the literature. In this report, we discuss a patient diagnosed with CFCS without the typical heart malformations but with craniofacial features, skin abnormalities, intellectual disability, and short stature. Genetic testing revealed the presence of three potentially harmful variants: one in the gene and two in the and genes, the significance of which is currently not yet found. Our findings in this case report suggest that the clinical symptoms of CFCS may be atypical, thereby expanding our understanding of the symptom spectrum of the disease. Simultaneously, the link between the clinical symptoms of the patient and the two unknown pathogenic variants has not been established. This case report supplements existing clinical reference material by providing valuable insights into the specific scenario.
Hsa_circ_0003489 Drives PTX Resistance of Human NSCLC Cells Through Modulating miR-98-5p/IGF2.
Xia S, Wang C
Pharmgenomics Pers Med · 2023 · PMID 37692338 · Full text
BACKGROUND: Circular RNAs (circRNAs) demonstrated critical roles within developing tumors and treatment resistance in an increasing body of research. The aim was to look into the functions and processes of hsa_circ_00034...
BACKGROUND: Circular RNAs (circRNAs) demonstrated critical roles within developing tumors and treatment resistance in an increasing body of research. The aim was to look into the functions and processes of hsa_circ_0003489 in the non-small cell lung cancer (NSCLC) paclitaxel (PTX) resistance. METHODS: NSCLC cell-based cultures including A549 and H460 were employed for such an investigation. hsa_circ_0003489, miR-98-5p, and insulin-like growth factor 2 (IGF2) expression-profiles were evaluated with a quantitative real-time polymerase chain reaction (RT-qPCR). The PTX resistance was determined using MTT assay, and the ELISA test measured IGF2 expression. Facilitating corroboration for miR-98-5p relation and hsa_circ_0003489 or IGF2, a dual-luciferase reporter method was applied. RESULTS: The hsa_circ_0003489 level was raised in cells and tissues from PTX-resistant (PR) NSCLC. In PR NSCLC cells, hsa_circ_0003489 knockdown reduced PTX resistance. For the purpose of the mechanism study, hsa_circ_0003489 knockdown substantially reduced IGF2 expression via miR-98-5p sponging, improving PTX sensitivity in PR NSCLC. CONCLUSION: Through miR-98-5p/IGF2 axis control, hsa_circ_0003489 knockdown helped NSCLC overcome PTX resistance, suggesting a potential circRNA-targeted therapy for the disease.
Pyroptosis and Inflammasome-Related Genes- and Polymorphisms Were Associated with Risk of Lung Cancer.
Jing X, Yun Y, Ji X … +2 more , Yang E, Li P
Pharmgenomics Pers Med · 2023 · PMID 37650010 · Full text
BACKGROUND: Cancer development and tumor immune microenvironment remodeling are closely linked to pyroptosis and inflammasome activation. However, little information is available in single nucleotide polymorphisms (SNPs)...
BACKGROUND: Cancer development and tumor immune microenvironment remodeling are closely linked to pyroptosis and inflammasome activation. However, little information is available in single nucleotide polymorphisms (SNPs) in pyroptosis and inflammasome-related genes in patients with lung cancer. This study aims to evaluate the associations between pyroptosis-related gene ( and ) polymorphisms and the risk of lung cancer. METHODS: The MassARRAY platform was used to genotype six SNPs of the and genes in 660 lung cancer cases and 660 controls. RESULTS: Individuals with rs35829419-A, rs385076-C, and rs775882-T alleles exhibited a higher risk of lung cancer ( < 0.01), while rs212704-T appears protective ( = 0.006). The rs35829419-AA, rs385076-TC/CC, and rs775882-CT/TT genotypes were associated with various degrees of elevated risk of lung cancer (<0.02), whereas rs212704-TT was associated with a reduced risk of the disease (=0.014). Genetic models analysis showed that rs35829419, rs385076, and rs775882 was associated with an increased risk of lung cancer, while rs212704 was related to a reduced risk in all three models ( < 0.05). The four SNPs remained significant in smoker and nonsmoker subgroups ( < 0.05). However, rs35829419 was correlated with risk of adenocarcinoma and small cell lung cancer, and rs212704 was only protective for squamous cell carcinoma. The rs385076 and rs775882 were associated with all three pathological types ( < 0.01). CONCLUSION: Besides providing candidate markers for identification of high-risk populations and early prevention of the disease, our research also provided new insight into anti-tumor strategies targeting inflammasomes and pyroptosis.
A Case-Control Study of the Relationship Between Genetic Polymorphism and Cretinism in Xinjiang.
Huang J, Wu H, Zhao G … +5 more , Ma Y, An Y, Sun L, Li F, Wang S
Pharmgenomics Pers Med · 2023 · PMID 37641720 · Full text
BACKGROUND: Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the developme...
BACKGROUND: Cretinism is a subtype of congenital hypothyroidism, an endocrine disorder resulting from inadequate thyroid hormone production or receptor deficiency. Genetic abnormalities play a major role in the development of thyroid dysfunction. METHODS: We recruited 183 participants with cretinism and 119 healthy participants from the Xinjiang Uyghur Autonomous Region and randomly selected 29 tag single nucleotide polymorphisms (tSNPs) in , and in all participants. We compared genotype and allele frequencies between cases and controls utilizing the chi-squared test, logistic regression analysis, and haplotype analysis. RESULTS: Using the chi-squared test, a single SNP was found to be associated with cretinism (recessive model: rs3754363, OR = 0.46, 95% CI = 0.27-0.80, P = 0.00519; genotype model: P = 0.01677). We stratified neurological, myxedematous, and mixed type and determined that another SNP was associated with a higher risk when comparing myxedematous type to the neurological type (rs2277923). CONCLUSION: rs3754363 has a statistically significant protective effect on people with cretinism, while rs2277923 may play a greater role in promoting the development of neurocretinism.
Clinical Characteristics and Novel Gene Mutation Analysis of Three Chinese Patients with Mowat-Wilson Syndrome.
Han X, Zhang Q, Wang C … +1 more , Han B
Pharmgenomics Pers Med · 2023 · PMID 37641719 · Full text
PURPOSE: Mowat-Wilson syndrome (MWS) is an autosomal dominant disease caused by a pathogenic variant of the gene. The main clinical manifestations include special facial features, Hirschsprung disease (HSCR), global dev...
PURPOSE: Mowat-Wilson syndrome (MWS) is an autosomal dominant disease caused by a pathogenic variant of the gene. The main clinical manifestations include special facial features, Hirschsprung disease (HSCR), global developmental delay and other congenital malformations. Here, we summarize the clinical characteristics and genetic mutation analysis of three Chinese patients with MWS. PATIENTS AND METHODS: The clinical characteristics of the patients were monitored and the treatment effect was followed up. DNA was extracted from peripheral blood and analyzed by sequencing. Whole exome sequencing was then performed. RESULTS: Three novel gene mutations were identified in 3 patients (c.1147_1150dupGAAC, p.Q384Rfs*7, c.1137_1146del TAGTATGTCT, p.S380Nfs *13 and c.2718delT, p.A907Lfs*23). They all had special facial features, intellectual disability, developmental delay, microcephaly, structural brain abnormalities and other symptoms. After long-term regular rehabilitation treatment, the development quotient of each functional area of the patient was slightly improved. CONCLUSION: Our study expanded the mutation spectrum of ZEB2 and enriched our understanding of the clinical features of MWS. It also shows that long-term standardized treatment is of great significance for the prognosis of patients.
Identification of Two Novel Variants of the Gene in Chinese Families with Duchenne Muscular Dystrophy.
Wu J, Ren L, Huang X … +6 more , Hu L, Zhang L, Xie D, Li Z, Han N, Huang S
Pharmgenomics Pers Med · 2023 · PMID 37609034 · Full text
BACKGROUND: Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the gene encoding a large structural protein in muscle cells. METHODS: Two probands, a 6-y...
BACKGROUND: Duchenne muscular dystrophy (DMD), an X-linked recessive neuromuscular disorder, is caused by pathogenic variants in the gene encoding a large structural protein in muscle cells. METHODS: Two probands, a 6-year old boy and a 1-month old infant, respectively, were clinically diagnosed with DMD based on elevated levels of creatine kinase and creatine kinase isoenzyme. CNVplex and whole exome sequencing (WES) were performed for causal variants, and Sanger sequencing was used for verification. RESULTS: CNVplex found no large deletions or duplications in the gene in both patients, but WES discovered a single-nucleotide deletion in exon 48 (NM_004006.2:c.6963del, p.Asp2322ThrfsTer16) in the proband of pedigree 1, and a nonsense mutation in exon 27 (NM_004006.2:c.3637A>T, p.K1213Ter) in the proband of pedigree 2. CONCLUSION: The results of our study expand the mutation spectrum of DMD and enrich our understanding of the clinical characteristics of DMD. Genetic counseling was provided for the two families involved in this study.
A Case Study and Literature Review of the Diagnosis of Danon Disease in Patients Presenting Only with Severe Cardiac Symptoms.
Sun YQ, Lv Q, Chen D … +3 more , Da Y, Zhao XY, Dong JZ
Pharmgenomics Pers Med · 2023 · PMID 37609033 · Full text
The clinical manifestations of Danon disease, which result from the primary deficiency of the lysosome-associated membrane protein 2 gene, include cardiomyopathy, skeletal myopathy, and different degrees of intellectual...
The clinical manifestations of Danon disease, which result from the primary deficiency of the lysosome-associated membrane protein 2 gene, include cardiomyopathy, skeletal myopathy, and different degrees of intellectual disability that vary greatly among patients. The present study reports on two cases of Danon disease in two patients who only presented cardiac symptoms. Cardiac symptoms usually occur in adolescence and during a patient's twenties, and most patients die from heart failure. However, the lab results from these cases suggested that other systems were involved, despite no other clinical symptoms. Significantly, the two patients had elevated serum cardiac troponin I, which often manifests in the acute cardiac phase, especially in severely affected patients with rapidly fatal outcomes. Danon disease is a multi-system involvement disease. Therefore, clinicians must be aware of its complexity when evaluating newly diagnosed patients due to its vastly different clinical course and prognosis and the importance of multidisciplinary management.
PSMC2 is a Novel Prognostic Biomarker and Predicts Immunotherapeutic Responses: From Pancreatic Cancer to Pan-Cancer.
Huang W, Qian Z, Shi Y … +5 more , Zhang Z, Hou R, Mei J, Xu J, Ding J
Pharmgenomics Pers Med · 2023 · PMID 37581119 · Full text
BACKGROUND: Proteasome 26S subunit ATPase 2 (PSMC2) is a part of the 19S regulatory complex, which catalyzes the unfolding and transport of substrates into the 20S proteasome. Our previous research demonstrated that PSMC...
BACKGROUND: Proteasome 26S subunit ATPase 2 (PSMC2) is a part of the 19S regulatory complex, which catalyzes the unfolding and transport of substrates into the 20S proteasome. Our previous research demonstrated that PSMC2 participates in the tumorigenesis and progression of pancreatic cancer (PC). However, no systematic analysis has been conducted to conclude its expression pattern and correlation with tumor immunity. AIM: To investigate the expression level of PSMC2 in PC, its prognostic value and its relationship with tumor immunity. METHODS: In numerous public and internal cohorts, the expression, prognostic significance, and immunological connections of PSMC2 in PC were investigated. Additionally, using data from The Cancer Genome Atlas (TCGA), a pan-cancer analysis was carried out to examine PSMC2's immunological assocaition, and the predictive power of PSMC2 for immunotherapy was also evaluated in numerous public cohorts. RESULTS: PSMC2 was overexpressed in tumor tissues and linked to unfavorable prognosis in PC. PSMC2 was not only positively correlated with TIICs, also positively correlated with immune checkpoints in PC. In addition to PC, PSMC2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, PSMC2 could predict the immunotherapeutic responses in various cancer types, including urothelial carcinoma and breast cancer. CONCLUSION: From PC to pan-cancer analysis, we report that PSMC2 is a novel prognostic biomarker in multiple cancer types. PSMC2 is related to the immuno-hot phenotype and predicts the outcome of immunotherapy. Therefore, the current study emphasizes that cancer patients with high PMSC2 expression should actively receive immunotherapy to improve their prognosis.
Pharmacogenetic Practice of Anticancer Drugs: Multiple Approaches for an Accurate and Comprehensive Genotyping.
Montrasio C, Cheli S, Clementi E
Pharmgenomics Pers Med · 2023 · PMID 37534027 · Full text
The application of pharmacogenetics in oncology is part of the routine clinical practice. In particular, genotyping of dihydropyrimidine dehydrogenase (DPYD) and UDP-glucuronosyltransferase (UGT1A1) is crucial to manage...
The application of pharmacogenetics in oncology is part of the routine clinical practice. In particular, genotyping of dihydropyrimidine dehydrogenase (DPYD) and UDP-glucuronosyltransferase (UGT1A1) is crucial to manage the treatment of patients taking fluoropyrimidines and irinotecan. The unique approach of our laboratory to the pharmacogenetic diagnostic service in oncology is to combine two real-time PCR methods, LightSNiP assay (TIB MOLBIOL), and more recently FRET (Fluorescent Resonance Energy Transfer) probes technology (Nuclear Laser Medicine), plus TaqMan assay (Thermo Fisher) for the confirmation of the presence of variant alleles on DNA from a second extraction. We found that both the FRET and LightSNiP assays, where detection occurs by melting curve analysis, offer an advantage over the competing TaqMan technology. Whereas unexpected genetic variants may be missed using a mutation-specific TaqMan assay, the information thus obtained can be useful to adjust the therapy in case of unexpected post-treatment toxicity. The combination of TaqMan and FRET assays helped us to achieve more accurate genotyping and a correct result for the patient. The added value of the DPYD FRET assay is the possibility of detecting, with the same amplification profile of the polymorphisms detailed in the guidelines, also the c.2194G>A (*6 rs1801160), cited in the recommendations as a variant to be investigated in case of severe toxicity. Regarding the UGT1A1 (TA)n promoter polymorphism (rs3064744), the distinctive and positive feature of the FRET assay is to allow clearly identifying all those potential variant alleles, including the (TA)5 and (TA)8 alleles, that are frequent in African Americans. Our clinical practice emphasizes the importance of not only rapid and easy-to-use assays, such as the new FRET ones, but also of accurate and comprehensive genotyping for good pharmacogenetic diagnostic activity.
Pharmacogenomics in the Management of Pulmonary Arterial Hypertension: Current Perspectives.
Coons JC, Empey PE
Pharmgenomics Pers Med · 2023 · PMID 37457231 · Full text
Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are currently 10 medications representative of five uni...
Pulmonary arterial hypertension (PAH) is a rare disease with heterogeneous causes that can lead to right ventricular (RV) failure and death if left untreated. There are currently 10 medications representative of five unique pharmacologic classes that are approved for treatment. These have led to significant improvements in overall clinical outcome. However, substantial variability in dosing requirements and treatment response is evident, leading to suboptimal outcome for many patients. Furthermore, dosing is empiric and iterative and can lead to delays in meeting treatment goals and burdensome adverse effects. Pharmacogenomic (PGx) associations have been reported with certain PAH medications, such as treprostinil and bosentan, and can explain some of the variability in response. Relevant genes associated with treprostinil include , and and are the genes encoding the major metabolizing liver enzymes for treprostinil, and reduced function variants (*2, *3) with were associated with lower treatment persistence. Additionally, a higher activity score was associated with a significantly less risk of treatment discontinuation. Other genes of interest that have been explored with treprostinil include , which is associated with right ventricular dysfunction and significantly higher dose requirements. Similarly, is associated with lower concentrations of cyclic adenosine monophosphate and significantly higher dose requirements. Genes of interest with the endothelin receptor antagonist (ERA) class include and . A genetic variant in (rs11157866) was linked to a significantly increased rate of clinical improvement with ERAs. The *2 variant with (encoding for the major metabolizing enzyme for bosentan) was significantly associated with a higher risk for elevations in hepatic aminotransferases and liver injury. In summary, this article reviews the relevant pharmacogenes that have been associated to date with dosing and outcome among patients who received PAH medications.
Association Between and Gene Polymorphisms and Stroke Susceptibility in the Chinese Han Population.
Zhang F, Peng H, Fu C … +8 more , Deng Y, Zhang M, Li W, Zhong J, Zhou Q, Huang L, Xiao S, Zhao J
Pharmgenomics Pers Med · 2023 · PMID 37441189 · Full text
BACKGROUND: Stroke has a high disability rate, and 30% of stroke cases have an unknown cause. Accurate diagnosis and treatment of stroke requires consideration of several rare heritable and non-heritable factors. OBJECTI...
BACKGROUND: Stroke has a high disability rate, and 30% of stroke cases have an unknown cause. Accurate diagnosis and treatment of stroke requires consideration of several rare heritable and non-heritable factors. OBJECTIVE: This study aimed to evaluate the impacts of three genetic polymorphisms (rs369149111 in , rs1803628 in and rs9808753 in ) on stroke susceptibility among the Chinese Han population. METHODS: Three single nucleotide polymorphisms (SNPs) from 623 stroke cases and 572 healthy controls were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the associations of three SNPs with stroke susceptibility. Additionally, SNP-SNP interactions were analyzed by multifactor dimensionality reduction (MDR). RESULTS: As demonstrated by the overall analysis, rs9808753 in (allele: OR = 1.25, 95% CI = 1.06-1.47, = 0.007; homozygous: OR = 1.59, 95% CI = 1.14-2.23, = 0.007; dominant: OR = 1.31, 95% CI = 1.02-1.67, = 0.032; recessive: OR = 1.42, 95% CI = 1.05-1.91, = 0.022; additive: OR = 1.26, 95% CI = 1.07-1.48, = 0.007) was associated with an increased susceptibility to stroke. Besides, stratification analysis suggested that rs9808753 was associated with an increased risk of stroke in subgroup aged ≤ 64 years, males and drinkers ( < 0.05). And rs1803628 in was significantly associated with an increased susceptibility to stroke in non-smokers ( < 0.05). CONCLUSION: A risk-increasing effect of rs980875 on stroke was detected in this study, which further broadens the understanding of the relationship between genetic polymorphisms and stroke susceptibility.
Impact of Variants on the Risk and Prognosis of Glioma in the Chinese Han Population.
Hu M, Wei J, Hao J … +2 more , Jin T, Li B
Pharmgenomics Pers Med · 2023 · PMID 37426899 · Full text
BACKGROUND: Glioma is the main pathological subtype of brain tumors with high mortality. OBJECTIVE: This study aimed to elucidate the correlation between variants and glioma risk in the Chinese Han population. METHODS:...
BACKGROUND: Glioma is the main pathological subtype of brain tumors with high mortality. OBJECTIVE: This study aimed to elucidate the correlation between variants and glioma risk in the Chinese Han population. METHODS: Genotyping of six variants of was completed by Agena MassARRAY platform in 1061 subjects (503 controls and 558 glioma patients). The relationship between polymorphisms and glioma risk was calculated using the logistic regression model, with odds ratio (OR) and 95% confidence intervals (CIs). A multifactor dimensionality reduction (MDR) method was performed to assess SNP-SNP interactions to predict glioma risk. RESULTS: In this research, overall analysis illustrated an association between rs9369269 and an increased risk of glioma. Rs9369269 was also related to the risk of glioma in patients aged ≤40 years and females. Subjects with rs9369269 AC genotype were likely to obtain glioma compared to people with CC genotype (patients with astroglioma vs healthy people). Compared to TT genotype carriers, carriers with AT genotype of rs1351835 were significantly associated with overall survival (OS). CONCLUSION: Taken together, the study identified the association between variants and glioma risk and variants were significantly associated with the prognosis of glioma. In the future, larger samples are needed to verify the results.
Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study.
Bollinger A, Stäuble CK, Jeiziner C … +5 more , Wiss FM, Hersberger KE, Lampert ML, Meyer Zu Schwabedissen HE, Allemann SS
Pharmgenomics Pers Med · 2023 · PMID 37426898 · Full text
PURPOSE: Pharmacogenetics (PGx) is an emerging aspect of personalized medicine with the potential to increase efficacy and safety of pharmacotherapy. However, PGx testing is still not routinely integrated into clinical p...
PURPOSE: Pharmacogenetics (PGx) is an emerging aspect of personalized medicine with the potential to increase efficacy and safety of pharmacotherapy. However, PGx testing is still not routinely integrated into clinical practice. We conducted an observational case series study where PGx information from a commercially available panel test covering 30 genes was integrated into medication reviews. The aim of the study was to identify the drugs that are most frequently object of drug-gene-interactions (DGI) in the study population. PATIENTS AND METHODS: In out-patient and in-patient settings, we recruited 142 patients experiencing adverse drug reaction (ADR) and/or therapy failure (TF). Collected anonymized data from the individual patient was harmonized and transferred to a structured database. RESULTS: The majority of the patients had a main diagnosis of a mental or behavioral disorder (ICD-10: F, 61%), of musculoskeletal system and connective tissue diseases (ICD-10: M, 21%), and of the circulatory system (ICD-10: I, 11%). The number of prescribed medicines reached a median of 7 per person, resulting in a majority of patients with polypharmacy (≥5 prescribed medicines, 65%). In total, 559 suspected DGI were identified in 142 patients. After genetic testing, an association with at least one genetic variation was confirmed for 324 suspected DGI (58%) caused by 64 different drugs and 21 different genes in 141 patients. After 6 months, PGx-based medication adjustments were recorded for 62% of the study population, whereby differences were identified in subgroups. CONCLUSION: The data analysis from this study provides valuable insights for the main focus of further research in the context of PGx. The results indicate that most of the selected patients in our sample represent suitable target groups for PGx panel testing in clinical practice, notably those taking drugs for mental or behavioral disorder, circulatory diseases, immunological diseases, pain-related diseases, and patients experiencing polypharmacy.
Are We Ready for Whole Population Genomic Sequencing of Asymptomatic Newborns?
Vears DF, Savulescu J, Christodoulou J … +2 more , Wall M, Newson AJ
Pharmgenomics Pers Med · 2023 · PMID 37415831 · Full text
The introduction of genomic sequencing technologies into routine newborn screening programs in some form is not only inevitable but also already occurring in some settings. The question is therefore not "if" but "when an...
The introduction of genomic sequencing technologies into routine newborn screening programs in some form is not only inevitable but also already occurring in some settings. The question is therefore not "if" but "when and how" genomic newborn screening (GNBS) should be implemented. In April 2022, the Centre for Ethics of Paediatric Genomics held a one-day symposium exploring ethical issues relating to the use of genomic sequencing in a range of clinical settings. This review article synthesises the panel discussion and presents both the potential benefits of wide-scale implementation of genomic newborn screening, as well as its practical and ethical issues, including obtaining appropriate consent, and health system implications. A more in-depth understanding of the barriers associated with implementing genomic newborn screening is critical to the success of GNBS programs, both from a practical perspective and also in order to maintain public trust in an important public health initiative.
Identification of Novel Prognostic Biomarkers That are Associated with Immune Microenvironment Based on GABA-Related Molecular Subtypes in Gastric Cancer.
Wang B, Huang L, Ye S … +2 more , Zheng Z, Liao S
Pharmgenomics Pers Med · 2023 · PMID 37405024 · Full text
BACKGROUND: Gamma-aminobutyric acid (GABA) plays an important role in tumorigenesis and progression. Despite this, the role of Reactome GABA receptor activation (RGRA) on gastric cancer (GC) remains unclear. This study w...
BACKGROUND: Gamma-aminobutyric acid (GABA) plays an important role in tumorigenesis and progression. Despite this, the role of Reactome GABA receptor activation (RGRA) on gastric cancer (GC) remains unclear. This study was intended to screen RGRA-related genes in GC and investigate their prognostic value. METHODS: GSVA algorithm was used to assess the score of RGRA. GC patients were divided into two subtypes based on the median score of RGRA. GSEA, functional enrichment analysis, and immune infiltration analysis were performed between the two subgroups. Then, differentially expressed analysis, and weighted gene co-expression network analysis (WGCNA) were used to identify RGRA-related genes. The prognosis and expression of core genes were analyzed and validated in the TCGA database, GEO database, and clinical samples. ssGSEA and ESTIMATE algorithms were used to assess the immune cell infiltration in the low- and high-core genes subgroups. RESULTS: High-RGRA subtype had a poor prognosis and activated immune-related pathways, as well as an activated immune microenvironment. ATP1A2 was identified to be the core gene. The expression of ATP1A2 was associated with the overall survival rate and tumor stage, and its expression was down-regulated in GC patients. Furthermore, ATP1A2 expression was positively correlated with the level of immune cells, including B cells, CD8 T cells, cytotoxic cells, DC, eosinophils, macrophages, mast cells, NK cells, and T cells. CONCLUSION: Two RGRA-related molecular subtypes were identified that could predict the outcome in GC patients. ATP1A2 was a core immunoregulatory gene and was associated with prognosis and immune cell infiltration in GC.
A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps.
Eken E, Estores DS, Cicali EJ … +2 more , Wiisanen KK, Johnson JA
Pharmgenomics Pers Med · 2023 · PMID 37383676 · Full text
Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabo...
Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of prior to prescribing PPIs. There are strong data to support the influence of genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.
Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis.
Zhao D, Qin D, Yin L … +1 more , Yang Q
Pharmgenomics Pers Med · 2023 · PMID 37383675 · Full text
BACKGROUND: Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated. METHOD...
BACKGROUND: Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated. METHODS: Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo. RESULTS: A total of 36 DEGs were identified. , and were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. , and were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of and decreased, whereas that of increased. Azathioprine treatment improved all the indicators to different degrees. CONCLUSION: , and are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.
The Association of Methylation Level in the Gene with High Altitude Pulmonary Edema in the Chinese Population.
Wang P, Lu H, Rong H … +6 more , Wang Y, Wang L, He X, Yuan D, He Y, Jin T
Pharmgenomics Pers Med · 2023 · PMID 37366513 · Full text
BACKGROUND: High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the a...
BACKGROUND: High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the association between methylation and HAPE. METHODS: Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of methylation with HAPE. DNA methylation site in the promoter region of was detected by Sequenom MassARRAY EpiTYPER platform. RESULTS: Probability analysis showed that the methylation probabilities of CYP39A1_1_CpG_5 and CYP39A1_3_CpG_21 are significant differences between the cases and controls (< 0.05). The methylation level analysis indicated that CYP39A1_1_CpG_2.3.4, CYP39A1_5_CpG_6.7, and CYP39A1_5_CpG_9.10 were higher methylation in HAPE compared to the controls (< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, = 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, = 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, = 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, = 0.033), and CYP39A1_5_CpG_20 (OR 3.05, = 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, = 0.016) and CYP39A1_3_CpG_21 (OR 0.18, = 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, = 0.014) and CYP39A1_3_CpG_21 (OR 0.08, = 0.023) had a protective impact on HAPE in people aged ≤32 years. CYP39A1_5_CpG_6.7 (OR 6.70, = 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, = 0.008) were related to an increased susceptibility to HAPE aged >32 years. Moreover, the diagnostic value of CYP39A1_3_CpG_21 (AUC = 0.712, < 0.001) was significantly better than other CpG sites. CONCLUSION: The methylation level of was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.
One Rare Warfarin Resistance Case and Possible Mechanism Exploration.
Zhao L, Zhai Z, Li P
Pharmgenomics Pers Med · 2023 · PMID 37359384 · Full text
One 59-year-old female patient with deep venous thrombosis (DVT) and pulmonary embolism (PE) was treated with 6 mg warfarin once daily as an anticoagulant. Before taking warfarin, her international normalized ratio (INR)...
One 59-year-old female patient with deep venous thrombosis (DVT) and pulmonary embolism (PE) was treated with 6 mg warfarin once daily as an anticoagulant. Before taking warfarin, her international normalized ratio (INR) was 0.98. Two days after warfarin treatment, her INR did not change from baseline. Due to the high severity of the PE, the patient needed to reach her target range (INR goal = 2.5, range = 2~3) rapidly, so the dose of warfarin was increased from 6 mg daily to 27 mg daily. However, the patient's INR did not improve with the dose escalation, still maintaining an INR of 0.97-0.98. We drew a blood sample half an hour before administering 27 mg warfarin and detected single nucleotide polymorphism for the following genes, which were identified to be relevant with warfarin resistance: CYP2C9 rs1799853, rs1057910, VKORC1 rs9923231, rs61742245, rs7200749, rs55894764, CYP4F2 rs2108622, and GGCX rs2592551. The trough plasma concentration of warfarin was 196.2 ng/mL after 2 days of warfarin administration with 27 mg QD, which was much lower than the therapeutic drug concentration ranges of warfarin (500-3,000 ng/mL). The genotype results demonstrate that the CYP4F2gene has rs2108622 mutation which can explain some aspect of warfarin resistance. Further investigations are necessary to fully characterize other pharmacogenomics or pharmacodynamics determinants of warfarin dose-response in Chinese.
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