Pharmacogenomics And Personalized Medicine[JOURNAL]
Sun
200 papers
What Personalized Medicine Humans Need and Way to It --also on the Practical Significance and Scientific Limitations of Precision Medicine.
Yuan B
Pharmgenomics Pers Med · 2022 · PMID 36353711 · Full text
The rise of precision medicine has opened up a broad space for the development of modern medicine and has also given practical significance to the concept of personalised medicine. Precision medicine is establishing a pe...
The rise of precision medicine has opened up a broad space for the development of modern medicine and has also given practical significance to the concept of personalised medicine. Precision medicine is establishing a personalized disease classification system that differs from the traditional system. However, the research progress of precision medicine in recent years is far from satisfactory: There are few disease types that can be attributed to the abnormality of a single target; the effects of current'precision' medications are not ideal, and various side effects remain unavoidable. The methodology of precision medicine is still reductionist, and it would not solve the integration problem of clinical treatment but rather would increase the difficulty of integration. Therefore, the precision medicine approach is not a feasible way to build a personalised medicine system. Based on the analysis and demonstration of the scientific limitations of precision medicine and the consistency of traditional Chinese medicine (TCM) and complexity science methods, this paper draws on the concepts and methods of cybernetics and complexity science, and proposes a fresh set of ideas and methods for the development of personalised medicine. The conclusion is as follows: Along the path of precision medicine, ideal personalised medicine cannot be achieved; what people ultimately need is personalised medicine that can achieve holistic integration. On the basis of TCM with the characteristics of holistic integration and personalisation, and according to scientific norms and the principle of evidence, building a theoretical model and state description system grounded in empirical evidence is the best way to establish a personalised medicine system.
Drug-Drug-Gene Interactions in Cardiovascular Medicine.
Asiimwe IG, Pirmohamed M
Pharmgenomics Pers Med · 2022 · PMID 36353710 · Full text
Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug-drug interactions, DDIs) and genomic factors (drug-gene interactions...
Cardiovascular disease remains a leading cause of both morbidity and mortality worldwide. It is widely accepted that both concomitant medications (drug-drug interactions, DDIs) and genomic factors (drug-gene interactions, DGIs) can influence cardiovascular drug-related efficacy and safety outcomes. Although thousands of DDI and DGI (aka pharmacogenomic) studies have been published to date, the literature on drug-drug-gene interactions (DDGIs, cumulative effects of DDIs and DGIs) remains scarce. Moreover, multimorbidity is common in cardiovascular disease patients and is often associated with polypharmacy, which increases the likelihood of clinically relevant drug-related interactions. These, in turn, can lead to reduced drug efficacy, medication-related harm (adverse drug reactions, longer hospitalizations, mortality) and increased healthcare costs. To examine the extent to which DDGIs and other interactions influence efficacy and safety outcomes in the field of cardiovascular medicine, we review current evidence in the field. We describe the different categories of DDIs and DGIs before illustrating how these two interact to produce DDGIs and other complex interactions. We provide examples of studies that have reported the prevalence of clinically relevant interactions and the most implicated cardiovascular medicines before outlining the challenges associated with dealing with these interactions in clinical practice. Finally, we provide recommendations on how to manage the challenges including but not limited to expanding the scope of drug information compendia, interaction databases and clinical implementation guidelines (to include clinically relevant DDGIs and other complex interactions) and work towards their harmonization; better use of electronic decision support tools; using big data and novel computational techniques; using clinically relevant endpoints, preemptive genotyping; ensuring ethnic diversity; and upskilling of clinicians in pharmacogenomics and personalized medicine.
The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review.
Wang J, Zhao YT, Sun MJ … +2 more , Chen F, Guo HL
Pharmgenomics Pers Med · 2022 · PMID 36349164 · Full text
High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma...
High-dose methotrexate (HDMTX) is a pivotal component of the chemotherapeutic regimens of osteosarcoma. However, the use of HDMTX is limited by an increased risk of dose-dependent toxicity. It is thought that the plasma levels and therapy-related toxicity of MTX could be associated with single nucleotide polymorphisms (SNPs) within MTX metabolism pathway genes. Here, we report a case of a paediatric osteosarcoma girl with delayed MTX excretion who was successfully managed using supportive measures and continuous veno-venous haemodiafiltration. We further identified the cause that could account for delayed elimination by genotyping analysis. The results showed that variations have been found in and , all those were reported to have a strong association with delayed elimination of MTX in clinical studies. After comprehensive consideration of genotype and clinical phenotype, the second course of HDMTX was administered to this patient at a half reduced dose. We also performed a literature review to summarize the pharmacogenetic factors that influence HDMTX pharmacokinetics or MTX-related adverse effects in osteosarcoma patients. It is suggested that the potential risk of delayed MTX elimination is worthy of clinical attention, and the implementation of genotyping should be considered to ensure therapeutic safety.
Mowat-Wilson Syndrome as a Differential Diagnosis in Patients with Congenital Heart Defects and Dysmorphic Facies.
Pachajoa H, Gomez-Pineda E, Giraldo-Ocampo S … +1 more , Lores J
Pharmgenomics Pers Med · 2022 · PMID 36345475 · Full text
Mowat-Wilson syndrome is a rare, autosomal dominant neurodevelopmental disorder characterized by distinctive facial gestalt and intellectual disability that is often associated with microcephaly, seizures and multiple co...
Mowat-Wilson syndrome is a rare, autosomal dominant neurodevelopmental disorder characterized by distinctive facial gestalt and intellectual disability that is often associated with microcephaly, seizures and multiple congenital anomalies, mainly heart defects. More than 350 patients and 180 genetic variants in the gene, have been reported with an estimated frequency of 1 per 70,000 births. Here we report a Colombian female patient with facial gestalt, intellectual disability, microcephaly, congenital heart defects, hypothyroidism and middle ear defect associated with the nonsense pathogenic variant c.2761C>T (p.Arg921Ter) in the gene. This case contributes to the understanding of the clinical complications and the natural history of this complex and clinically heterogeneous disorder but also to the awareness that patients with heart congenital defects and dysmorphic facies may present an underlying genetic disorder.
Neurofibromatosis Type 1 and Hypospadias in a Male 46, XY with a Mutation in the Gene and a Mutation in .
Perafan-Valdes L, Giraldo-Ocampo S, Lores J … +1 more , Pachajoa H
Pharmgenomics Pers Med · 2022 · PMID 36317063 · Full text
Neurofibromatosis type 1 is one of the most common genetic autosomal dominant disorders described, with a prevalence of 1 in 2000 to 1 in 3000 individuals. It is characterized by skin, nerves, and bone abnormalities. Non...
Neurofibromatosis type 1 is one of the most common genetic autosomal dominant disorders described, with a prevalence of 1 in 2000 to 1 in 3000 individuals. It is characterized by skin, nerves, and bone abnormalities. Non-related to NF1, hypospadias is a displacement in the urethral opening which in the majority of patients has an idiopathic cause. Here, we describe a patient with neurofibromatosis type 1, hypospadias, and unilateral cryptorchidism. The heterozygous variants c.6789_6792delTTAC, p.(Tyr2264Thrfs*5) and c.140A>G, p.(Tyr47Cys) were found in the and genes, respectively. This case contributes to the phenotypical characterization of patients with NF1 but also with hypospadias caused by a mutation in the gene, which usually leads to severe sex disorders.
Shwachman Diamond Syndrome with Arrhythmia as the First Manifestation a Case Report and Literature Review.
Yu H, Zhao W, Ni Y … +1 more , Li L
Pharmgenomics Pers Med · 2022 · PMID 36254235 · Full text
OBJECTIVE: Analyze the different clinical manifestations and genetic characteristics of Shwachman diamond syndrome (SDS). METHODS: The clinical data of a case of neonatal onset Shwachman diamond syndrome with arrhythmia...
OBJECTIVE: Analyze the different clinical manifestations and genetic characteristics of Shwachman diamond syndrome (SDS). METHODS: The clinical data of a case of neonatal onset Shwachman diamond syndrome with arrhythmia as the first manifestation were retrospectively analyzed, and the relevant literature was reviewed to summarize the clinical manifestations, genetic characteristics and treatment of Shwachman diamond syndrome. RESULTS: The patient, female, age 1 month 24 days, with ventricular arrhythmia as the first manifestation, accompanied by growth retardation, liver damage, and persistent decrease in peripheral blood neutrophil count (< 1.5 × 10/l), no pancreatic exocrine gland dysfunction at the initial stage of the disease. Gene detection showed that the SBDS gene chr7:66,459,197, c.258+2T > C homozygous variation. CONCLUSION: Although the classic manifestations of Shwachman diamond syndrome are pancreatic exocrine insufficiency, pancreatic adiposis and unexplained neutropenia, its clinical manifestations are complex and diverse, involving multiple systems. For suspected children, early genetic examination is helpful for subsequent diagnosis and treatment.
Downregulation of Crystallin Lambda 1 is a New Independent Prognostic Marker in Clear Cell Renal Cell Carcinoma.
Feng L, Ding G, Zhou Y … +2 more , Zhu H, Jiang H
Pharmgenomics Pers Med · 2022 · PMID 36246497 · Full text
BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer subtype, has a high mortality rate. Crystallin lambda 1 (CRYL1) encodes an enzyme that catalyzes the dehydrogenation of L-gulonate int...
BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most prevalent kidney cancer subtype, has a high mortality rate. Crystallin lambda 1 (CRYL1) encodes an enzyme that catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in uronate cycle. CRYL1 dysregulation has been linked to the progression of several cancers. This research aimed to evaluate the prognostic significance of CRYL1 expression in ccRCC prognosis. METHODS: Clinical data and gene expression profiles on ccRCC were retrieved from the University of California Santa Cruz Xena platform. Differences (variations) in the expression profiles of CRYL1 in ccRCC and healthy tissues were found using RNA-sequencing data, and these findings were validated using qPCR with real-world samples. CRYL1 expression levels were also linked to clinicopathological characteristics, survival, and immune microenvironments. The potential pathway via which CRYL1 expression levels impact the prognosis of patients with ccRCC was investigated using gene set enrichment analysis (GSEA). RESULTS: In ccRCC tissues, CRYL1 expression levels were lower compared to healthy renal tissues in TCGA cohort (n = 535, < 0.001), which was validated in another real-world cohort (n = 14, < 0.001). Lower CRYL1 expression levels were linked to unfavorable clinicopathological characteristics and prognoses ( < 0.001). According to multivariate Cox regression analysis (P < 0.001), CRYL1 expression levels in patients with ccRCC could serve as an independent prognostic indicator. Furthermore, a strong link between CRYL1 expression levels and immune microenvironment was observed ( < 0.001). Finally, GSEA revealed that CRYL1 expression levels (P < 0.001) were associated with fatty acid metabolism, G2M checkpoint delays, and epithelial-mesenchymal transitions in ccRCC. CONCLUSION: Our study found that lower levels of CRYL1 expression were linked to unfavorable clinicopathological characteristics and worse prognoses, and CRYL1 could serve as a new target for the treatment of ccRCC, which is useful for personalized medicine.
Contribution of Polymorphisms to Esophageal Cancer Risk Among the Chinese Han Population.
Yu S, Yuan G, Hu F … +6 more , Li Y, Chen Z, Zhang R, Li P, Chen Z, Song J
Pharmgenomics Pers Med · 2022 · PMID 36172401 · Full text
BACKGROUND: was overexpressed in esophageal cancer (EC). The study aimed to identify genotypes of polymorphisms and their correlation with EC occurrence in a Chinese Han population. METHODS: Four single nucleotide poly...
BACKGROUND: was overexpressed in esophageal cancer (EC). The study aimed to identify genotypes of polymorphisms and their correlation with EC occurrence in a Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) in were randomly selected for genotyping through Agena MassARRAY system among 525 EC patients and 522 healthy controls. Multiple genetic models were applied to assess the association of polymorphisms with EC susceptibility by calculating odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Rs10934270 was associated with lower EC susceptibility (OR = 0.64, = 0.004) with statistical power >90% in overall analysis. Specifically, the correlation of rs10934270 with EC susceptibility was found in subgroups including patients with esophageal squamous cell carcinoma (ESCC), males, subjects aged ≤65 years, subjects with BMI ≤ 24 kg/m, and smokers. Rs9841504 might be a risk-increasing factor for ESCC. Moreover, rs9288999 in subjects aged ≤65 years and rs73230612 in females were related to lower EC risk. CONCLUSION: Our research is the first to report that rs10934270 is associated with reduced EC susceptibility in the Chinese Han population. These data provide a scientific basis for understanding the influence of the gene on EC occurrence.
Association of and Polymorphisms with Type 2 Diabetes in the Chinese Han Populations.
Zhang L, Tang J, Wang Y … +2 more , Wang X, Wang F
Pharmgenomics Pers Med · 2022 · PMID 36168322 · Full text
BACKGROUND: Type 2 diabetes mellitus (T2DM) is caused by diverse environmental and genetic risk factors. Previous studies have reported that cytochrome P450 () is a promising gene for T2DM. Therefore, we aimed to determi...
BACKGROUND: Type 2 diabetes mellitus (T2DM) is caused by diverse environmental and genetic risk factors. Previous studies have reported that cytochrome P450 () is a promising gene for T2DM. Therefore, we aimed to determine the effects of and polymorphisms on T2DM susceptibility among the Chinese Han population. METHODS: A case-control study was conducted to assess the potential relationship of four polymorphisms (rs8192879, rs12542233, rs2070672 and rs2515641) with T2DM susceptibility in the Chinese population, involving 512 T2DM patients and 515 age- and gender-matched healthy individuals. We used the Agena MassARRAY platform to detect and polymorphisms. The relationship between genetic polymorphisms and T2DM risk was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models. RESULTS: After adjusting for age and gender, rs12542233 in the gene was significantly associated with decreased T2DM risk (recessive: OR = 0.67, 95% CI = 0.49-0.91, = 0.012; after FDR correction, = 0.048). The rs12542233 was associated with a reduced risk of T2DM in people over 59 years of age ( = 0.010). In the population with BMI ≤ 24 kg/m, rs12542233 was associated with an increased risk of T2DM ( < 0.05). In the population with BMI > 24 kg/m, rs2515641 can significantly reduce the risk of T2DM ( < 0.05). And rs8192879, rs2070672 and rs2515641 could significantly increase the risk of diabetes retinopathy in T2DM patients ( < 0.05). Furthermore, the TC haplotype was significantly associated with T2DM ( = 0.019). CONCLUSION: and polymorphisms may contribute to T2DM susceptibility in the Chinese Han population, especially in stratified analysis.
The Association Between Genetic Polymorphisms of Transporter Genes and Prognosis of Platinum-Based Chemotherapy in Lung Cancer Patients.
He J, Wang Z, Zou T … +3 more , Wang Y, Li XP, Chen J
Pharmgenomics Pers Med · 2022 · PMID 36131844 · Full text
OBJECTIVE: Platinum-based chemotherapy is the first-line treatment of lung cancer. However, different individual and genetic variation effect therapy for lung cancer. The purpose of this study was to evaluate the associa...
OBJECTIVE: Platinum-based chemotherapy is the first-line treatment of lung cancer. However, different individual and genetic variation effect therapy for lung cancer. The purpose of this study was to evaluate the association between transport genes genetic polymorphisms and the prognosis of platinum-based chemotherapy in lung cancer patients. METHODS: A series of 593 patients with treatment of platinum-based chemotherapy were recruited for this study. A total of 21 single-nucleotide polymorphisms in nine transporter genes were selected to investigate their associations with platinum-based chemotherapy prognosis. RESULTS: Patients with ABCG2 rs1448784 CC genotype had a significantly shorter PFS than CT or TT genotypes (Additive model: HR = 1.54, 95% CI = 1.02-2.35, = 0.040). In stratification analysis, SLC22A2 rs316003, SLC2A1 rs4658 were related to PFS and AQP9 rs1867380, SLC2A1 rs3820589, SLC22A2 rs316003 indicated were related to OS of platinum-based chemotherapy prognosis. CONCLUSION: Genetic polymorphisms of rs1448784 in ABCG2 might be potential clinical marker for predicting the prognosis of lung cancer patients treated with platinum-based chemotherapy.
IL-10 rs1800896 Polymorphism: A Risk Factor for Adult Acute Lymphoblastic Leukemia.
Abdalhabib EK, Alzahrani B, Saboor M … +9 more , Hamza A, Elfaki EM, Alanazi F, Alenazy FO, Algarni A, Khider Ibrahim I, Mohamed HA, Hussein Alfeel A, Ali Alshaikh N
Pharmgenomics Pers Med · 2022 · PMID 36119849 · Full text
PURPOSE: Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10...
PURPOSE: Single-nucleotide polymorphism (SNP) in the promoter region of the IL-10 gene can increase susceptibility to tumor development. The current study aimed to explore the genotypic frequency of interleukin-10 (IL-10) rs1800896 polymorphism in newly diagnosed adult patients with acute lymphoblastic leukemia (ALL) and validate whether this SNP is a risk factor for adult ALL. PATIENTS AND METHODS: This case-control study was based on a subset of newly diagnosed 154 adult patients with ALL recruited from the Radiation and Isotope Center in Khartoum (RICK) and 154 healthy controls from the same geographical area. Genomic DNA was used for the genotyping of rs1800896 polymorphism through allele-specific polymerase chain reaction (PCR) assays. RESULTS: The genotypic frequencies of rs1800896 showed a statistically significant association of AG and AA genotypes with adult ALL (<0.001). Combined genotypes AG+GG vs AA also showed a positive association of rs1800896 with adult ALL (OR=4.89). The allelic frequencies of G and A did not show any significant difference in adult patients with ALL compared with the control group. AG rs1800896 genotype showed an increased risk of B and T ALL (OR=2.51 and 4.70, respectively). Age at diagnosis, gender, and immunophenotype (B vs T ALL) did not exhibit any association of rs1800896 with ALL in this patient group. CONCLUSION: rs1800896 polymorphism is associated with an increased risk of ALL in adult patients irrespective of the age at diagnosis, gender, and immunophenotype of ALL.
and Variants Were Correlated with Alcohol-Induced Femoral Head Necrosis Risk in the Chinese Han Population.
Liu C, Liu X, Li X
Pharmgenomics Pers Med · 2022 · PMID 36110408 · Full text
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common joint disease caused by excessive drinking, genetic factors, etc. The purpose of this study was to investigate the association between and variants and a...
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a common joint disease caused by excessive drinking, genetic factors, etc. The purpose of this study was to investigate the association between and variants and alcohol-induced ONFH (AIONFH) risk in the Chinese Han population. METHODS: This study genotyped 9 selected single nucleotide polymorphisms (SNPs) in 402 males by Agena MassARRAY Assay. By calculating odds ratios (ORs) and 95% confidence intervals (CIs), we assessed the effect of gene polymorphisms on AIONFH occurrence. False-positive report probability (FPRP) analysis and power were also used to evaluate the significant results. Multifactor dimensionality reduction (MDR) software was also utilized to predict the association between the selected SNPs and AIONFH risk. RESULTS: The overall analysis showed that rs10903966 and rs7320969 were correlated with AIONFH risk. rs4773724 was associated with a reduced risk of AIONFH, while individuals with rs9523981 CC genotype had a higher risk of AIONFH than individuals with the other genotypes among people under 42 years old. Based on stratified analysis of necrotic sites, rs7320969 was related to a decreased risk of AIONFH, while rs10903966 and rs9523981 were related to an increased risk of AIONFH. In addition, rs1008993 and rs7320969 were observed to be linked to AIONFH risk in patients at different clinical stages. Meanwhile, there were significant differences in TC, TG, platelet, ApoA1 and ApoB levels among subjects with different genotypes of rs1008993, rs9523981, rs7320969 and rs59624626. The results of MDR showed that rs11251720 and rs7320969 may play a synergistic role in predicting the risk of AIONFH. CONCLUSION: rs10903966 and rs9523981 were associated with an increased risk of AIONFH, while GPC6 (rs7320969 and rs4773724) were correlated with a decreased risk of AIONFH. This result will need further experiments to verify.
Expression Profile and Bioinformatics Analysis of Circular RNAs in Patients with Vitiligo.
Zhang R, Hou Z, Liao K … +3 more , Yu C, Jing R, Tu C
Pharmgenomics Pers Med · 2022 · PMID 36092681 · Full text
PURPOSE: Circular RNAs (circRNAs) are abundant, stable, and evolutionarily conserved noncoding RNAs with impacts on cell proliferation, differentiation, invasion, apoptosis, and immunity by acting as an miRNA sponge. Thi...
PURPOSE: Circular RNAs (circRNAs) are abundant, stable, and evolutionarily conserved noncoding RNAs with impacts on cell proliferation, differentiation, invasion, apoptosis, and immunity by acting as an miRNA sponge. This study aimed to investigate the expression of circRNAs in vitiligo and analyze the differentially expressed circRNAs (DEcircRNAs) bioinformatically. PATIENTS AND METHODS: Biopsies of five lesional and five nonlesional skins of patients with vitiligo and five healthy skins (control) were harvested in this study. The expression profiles of circRNAs and DEcircRNAs were determined by microarray analysis and qRT-PCR. Bioinformatics analysis was used to predict target genes of DEcircRNAs binding to miRNAs and their underlying functions. Meanwhile, a competing endogenous RNA (ceRNA) network was constructed using Cytoscape. RESULTS: A total of 817 and 508 DEcircRNAs were identified in lesional and nonlesional skins of patients with vitiligo, respectively. The results of hsa_circRNA_000957 and hsa_circRNA_101798 validation were consistent with our microarray analysis. Furthermore, 32 miRNA response elements (MREs) and related target genes of DEcircRNAs were identified, whose main functions were involved in the pathogenesis of vitiligo. Hsa_circRNA_000957 and hsa_circRNA_101798 might be candidate biomarkers for vitiligo. CONCLUSION: This study provides scientific clues for understanding the mechanism of vitiligo.
Risk Factors and Predictive Model for Dermatomyositis Associated with Rapidly Progressive Interstitial Lung Disease.
Wang K, Tian Y, Liu S … +4 more , Zhang Z, Shen L, Meng D, Li J
Pharmgenomics Pers Med · 2022 · PMID 36071824 · Full text
BACKGROUND: Rapidly progressive interstitial lung disease (RP-ILD) is a significant complication that determines the prognosis of dermatomyositis (DM). Early RP-ILD diagnosis can improve screening and diagnostic efficien...
BACKGROUND: Rapidly progressive interstitial lung disease (RP-ILD) is a significant complication that determines the prognosis of dermatomyositis (DM). Early RP-ILD diagnosis can improve screening and diagnostic efficiency and provide meaningful guidance to carry out early and aggressive treatment. METHODS: A retrospective screening of 284 patients with DM was performed. Clinical and laboratory characteristics of the patients were recorded. The risk factors of RP-ILD in DM patients were screened by logistic regression (LR) and machine learning methods, and the prediction models of RP-ILD were developed by machine learning methods, namely least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (XGBoost). RESULTS: According to the result of univariate LR, disease duration is a protective factor for RP-ILD, and ESR, CRP, anti-Ro-52 antibody and anti-MDA5 antibody are risk factors for RP-ILD. The top 10 important variables of the 3 machine learning models were intersected to obtain common important variables, and there were 5 common important variables, namely disease duration, LDH, CRP, anti-Ro-52 antibody and anti-MDA5 antibody. The AUC of LASSO, RF and XGBoost test set were 0.661, 0.667 and 0.867, respectively. We further validated the performance of these three models on validation set, and the results showed that, the AUC of LASSO, RF and XGBoost were 0.764, 0.727 and 0.909, respectively. Based on the results of the models, XGBoost is the optimal model in this study. CONCLUSION: Disease duration, LDH, CRP, anti-Ro-52 antibody and anti-MDA5 antibody are vital risk factors for RP-ILD in DM. The prediction model constructed using XGBoost can be used for risk identification and early intervention in DM patients with RP-ILD and practical application.
Prescription Advice Based on Data of Drug-Drug-Gene Interaction of Patients with Polypharmacy.
Salamone S, Spirito S, Simmaco M … +5 more , Unger M, Preissner S, Gohlke BO, Eckert A, Preissner R
Pharmgenomics Pers Med · 2022 · PMID 36004008 · Full text
PURPOSE: Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medicati...
PURPOSE: Pharmacogenetic counselling is a complex task and requires the efforts of an interdisciplinary team, which cannot be implemented in most cases. Therefore, simple rules could help to minimize the risk of medications incompatible with each other or with frequent genetic variants. PATIENTS AND METHODS: One hundred and eighty-four multi-morbid Caucasian patients suffering from side effects or inefficient therapy were enrolled and genotyped. Their medication was analyzed by a team of specialists using Drug-PIN (medication support system) and individual recommendations for 34 drug classes were generated. RESULTS: In each of the critical drug classes, 50% of the drugs cannot be recommended to be prescribed in typical drug cocktails. PPIs and SSRI/SNRIs represent the most critical drug classes without showing a single favorable drug. Among the well-tolerated drugs (not recommended for less than 5% of the patients) are metamizole, celecoxib, olmesartan and famotidine. For each drug class, a ranking of active ingredients according to their suitability is presented. CONCLUSION: Genotyping and its profound analysis are not available in many settings today. The consideration of frequent alterations of metabolic elimination routes and drug-drug-gene interactions by using simple rankings can help to avoid many incompatibilities, side effects and inefficient therapies.
Genome-Wide Association Study on the Hematological Phenotypic Characteristics of the Han Population from Northwest China.
Yang W, He X, Yao Y … +8 more , Lu H, Wang Y, Zhang Z, Wang Y, Wang L, He Y, Yuan D, Jin T
Pharmgenomics Pers Med · 2022 · PMID 35945964 · Full text
BACKGROUND: Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematologi...
BACKGROUND: Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China. METHODS: A genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV ( < 5E-7) was then selected for replication detection. RESULTS: Ninety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) ( = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content ( = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype ( = 0.023). CONCLUSION: The GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.
Cuproptosis-Related Gene - and - Polymorphisms are Associated with Risk of Lung Cancer.
Yun Y, Wang Y, Yang E … +1 more , Jing X
Pharmgenomics Pers Med · 2022 · PMID 35923305 · Full text
BACKGROUND: Cuproptosis is a novel copper-dependent cell death, and the copper level was increased in lung cancer patients. However, few studies evaluated the association between single-nucleotide polymorphisms (SNPs) in...
BACKGROUND: Cuproptosis is a novel copper-dependent cell death, and the copper level was increased in lung cancer patients. However, few studies evaluated the association between single-nucleotide polymorphisms (SNPs) in cuproptosis-related genes and lung cancer risk. METHODS: Six SNPs of the and genes were genotyped in a case-control cohort including 650 lung cancer cases and 650 controls using the MassARRAY platform. RESULTS: The minor alleles of -rs10981694 and -rs10488764 were associated with an increased risk of lung cancer (rs10981694: OR=1.455, 95% CI: 1.201-1.763, <0.001; rs10488764: OR=1.483, 95% CI: 1.244-1.768, <0.001). In contrast, the minor alleles of rs9535826 and rs9535828 in were related to a decreased risk of the disease (rs9535826: OR=0.714, 95% CI: 0.608-0.838 <0.001; rs9535828: OR=0.679, 95% CI: 0.579-0.796, <0.001). The frequencies of rs10981694-TG/GG and rs10488764-GA/AA genotypes were significantly higher in lung cancer cases than that in controls, making them risk genotypes for the disease ( < 0.001); while the rs9535826-TG/GG and rs9535828-GA/AA genotypes were protective genotypes and associated with a reduced risk of the disease (<0.001). Genetic model evaluation revealed that -rs10981694 and -rs10488764 were associated with a growing risk of lung cancer in dominant, recessive and log-additive models (<0.001). Moreover, rs9535826 and rs9535828 in were related to a declining risk of the disease in three genetic models (<0.001). In addition, stratification analysis showed that -rs10488764 was risk variant for lung cancer in both smokers and nonsmokers, and was associated with risk of each pathological type of lung cancer (<0.008). CONCLUSION: The results shed new light on the correlation between cuproptosis-related genes and risk of lung cancer.
A Study on the Molecular Mechanism of High Altitude Heart Disease in Children.
Tashi QZ, Tsering SB, Zhou NN … +4 more , Zhang Y, Huang YJ, Jia J, Li TJ
Pharmgenomics Pers Med · 2022 · PMID 35903087 · Full text
OBJECTIVE: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common...
OBJECTIVE: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD. METHODS: First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau. RESULTS: With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO. CONCLUSION: The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.
Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder.
Alhazmi S, Alzahrani M, Farsi R … +14 more , Alharbi M, Algothmi K, Alburae N, Ganash M, Azhari S, Basingab F, Almuhammadi A, Alqosaibi A, Alkhatabi H, Elaimi A, Jan M, Aldhalaan HM, Alrafiah A, Alrofaidi A
Pharmgenomics Pers Med · 2022 · PMID 35898556 · Full text
INTRODUCTION: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD...
INTRODUCTION: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD. METHODS: This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing. RESULTS: The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control. CONCLUSION: CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.
Identification of a Novel Variant in a Patient with Primary Ciliary Dyskinesia.
Yang B, Lei C, Yang D … +6 more , Lu C, Xu Y, Wang L, Guo T, Wang R, Luo H
Pharmgenomics Pers Med · 2022 · PMID 35847568 · Full text
BACKGROUND: encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. was reported to be associated with X-chromosome linked dysmorphology syndrome in...
BACKGROUND: encodes a protein with 1012 amino acids, which is a component of basal bodies and centrioles, essential for cilia biogenesis. was reported to be associated with X-chromosome linked dysmorphology syndrome in early studies and recent studies reported a few cases with primary ciliary dyskinesia (PCD) caused by deficiency. CASE PRESENTATION: We report a 31-year-old man who suffered from recurrent respiratory infections with typical manifestations of primary ciliary dyskinesia. In addition to respiratory manifestations, the patient also had situs inversus, obesity, gastroesophageal reflux, and hearing impairment. Clubbing fingers and mild streblomicrodactyly were also observed. EXAMINATION RESULT: We performed whole-exome sequencing to identify a novel variant c.2795delA:p.(Lys932Argfs*3) in . The hemizygous variant was predicted to be likely pathogenic by bioinformatic analysis software and ACMG guideline. High-speed video microscopy (HSVM), transmission electron microscopy (TEM), and immunofluorescence were performed to analyze the respiratory cilia. A high beating frequency and a stiff beating pattern were observed under HSVM, while there were no significant abnormalities in TEM and immunofluorescence. The sperm flagella examinations were also generally normal. CONCLUSION: Our study identified a novel frameshift variant in causing PCD, enriched the genetic spectrum of variants, and verified that mutation can lead to only a PCD characteristic phenotype, while other -associated syndromic symptoms such as dysmorphic features and renal symptoms were not present.
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