Pharmacogenomics and Personalized Medicine最新文献

{"title":"The Single Nucleotide Polymorphisms of AP1S1 are Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Population.","authors":"Feng Su,&nbsp;Yong Fang,&nbsp;Jinjie Yu,&nbsp;Tian Jiang,&nbsp;Siyun Lin,&nbsp;Shaoyuan Zhang,&nbsp;Lu Lv,&nbsp;Tao Long,&nbsp;Huiwen Pan,&nbsp;Junqing Qi,&nbsp;Qiang Zhou,&nbsp;Weifeng Tang,&nbsp;Guowen Ding,&nbsp;Liming Wang,&nbsp;Lijie Tan,&nbsp;Jun Yin","doi":"10.2147/PGPM.S342743","DOIUrl":"https://doi.org/10.2147/PGPM.S342743","url":null,"abstract":"<p><strong>Background: </strong>The σ1A subunit of the adaptor protein 1 (AP1S1) participates in various intracellular transport pathways, especially the maintenance of copper homeostasis, which is pivotal in carcinogenesis. It is therefore rational to presume that AP1S1 might also be involved in carcinogenesis. In this hospital-based case-control study, we investigated the genetic susceptibility to ESCC in relation to SNPs of <i>AP1S1</i> among Chinese population.</p><p><strong>Methods: </strong>A database containing a total of 1303 controls and 1043 ESCC patients were retrospectively studied. The <i>AP1S1</i> SNPs were analyzed based on ligation detection reaction (LDR) method. Then, the relationship between ESCC and SNPs of AP1S1 was determined with a significant crude P<0.05. Then the logistic regression analysis was used for the calculation for adjusted P in the demographic stratification comparison if a significant difference was observed in the previous step.</p><p><strong>Results: </strong><i>AP1S1</i> rs77387752 C>T genotype TT was an independent risk factor for ESCC, while rs4729666 C>T genotype TC and rs35208462 C>T genotype TC were associated with a lower risk for ESCC, especially in co-dominant model and allelic test for younger, male subjects who are not alcohol-drinkers nor cigarette smokers.</p><p><strong>Conclusion: </strong><i>AP1S1</i> rs77387752, rs4729666 and rs35208462 polymorphisms are associated with susceptibility to ESCC in Chinese individuals. <i>AP1S1</i> SNPs may exert an important role in esophageal carcinogenesis and could serve as potential diagnostic biomarkers.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"235-247"},"PeriodicalIF":1.9,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/90/pgpm-15-235.PMC8938157.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40317550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Value of UGT2B7-161 Single Nucleotide Polymorphism in Predicting the Risk of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Who Underwent Pertuzumab Combined with Trastuzumab Therapy by PSL.","authors":"Jian Li,&nbsp;Hui Luo,&nbsp;Ying-Ying Liu,&nbsp;Li-Xin Chen,&nbsp;Mei-Qin Zhu,&nbsp;Quan-Tong Deng,&nbsp;Dong-Mei Zhu,&nbsp;Zi-Mo Wang,&nbsp;Jin-Feng Xu","doi":"10.2147/PGPM.S351718","DOIUrl":"https://doi.org/10.2147/PGPM.S351718","url":null,"abstract":"<p><strong>Objective: </strong>To explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy.</p><p><strong>Methods: </strong>Fifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury.</p><p><strong>Results: </strong>There were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity.</p><p><strong>Conclusion: </strong>UGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"215-225"},"PeriodicalIF":1.9,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a8/7d/pgpm-15-215.PMC8935087.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40317549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.","authors":"Ezeldine K Abdalhabib,&nbsp;Badr Alzahrani,&nbsp;Fehaid Alanazi,&nbsp;Abdulrahman Algarni,&nbsp;Ibrahim Khider Ibrahim,&nbsp;Hozifa A Mohamed,&nbsp;Hassan A Hamali,&nbsp;Abdullah A Mobarki,&nbsp;Gasim Dobie,&nbsp;Muhammad Saboor","doi":"10.2147/PGPM.S356302","DOIUrl":"https://doi.org/10.2147/PGPM.S356302","url":null,"abstract":"<p><strong>Purpose: </strong>Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of <i>GSTT1</i>, and <i>GSTM1</i> polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.</p><p><strong>Patients and methods: </strong>This case-control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of <i>GSTT1</i> and <i>GSTM1</i> genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.</p><p><strong>Results: </strong>The genotypic frequency of <i>GSTT1</i> null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of <i>GSTM1</i> null polymorphism in cases and controls (OR = 3.7, P = <0.001). Combined <i>GSTT1</i> null and <i>GSTM1</i> null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42-29.74, P < 0.001).</p><p><strong>Conclusion: </strong>Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"227-234"},"PeriodicalIF":1.9,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/23/pgpm-15-227.PMC8934168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40310676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Drug-Metabolizing Enzyme and Transporter Gene Polymorphisms and Lipid-Lowering Response to Statins in Thai Patients with Dyslipidemia.","authors":"Natchaya Vanwong,&nbsp;Sayanit Tipnoppanon,&nbsp;Chalitpon Na Nakorn,&nbsp;Pornpen Srisawasdi,&nbsp;Punyanuch Rodcharoen,&nbsp;Sadeep Medhasi,&nbsp;Pajaree Chariyavilaskul,&nbsp;Sarawut Siwamogsatham,&nbsp;Yongkasem Vorasettakarnkij,&nbsp;Chonlaphat Sukasem","doi":"10.2147/PGPM.S346093","DOIUrl":"https://doi.org/10.2147/PGPM.S346093","url":null,"abstract":"<p><strong>Purpose: </strong>Statins are increasingly widely used in the primary and secondary prevention of cardiovascular disease. However, there is an inter-individual variation in statin response among patients. The study aims to determine the association between genetic variations in drug-metabolizing enzyme and transporter (DMET) genes and lipid-lowering response to a statin in Thai patients with hyperlipidemia.</p><p><strong>Patients and methods: </strong>Seventy-nine patients who received statin at steady-state concentrations were recruited. Serum lipid profile was measured at baseline and repeated after 4-month on a statin regimen. The genotype profile of 1936 DMET markers was obtained using Affymetrix DMET Plus genotyping microarrays.</p><p><strong>Results: </strong>In this DMET microarray platform, five variants; <i>SLCO1B3</i> (rs4149117, rs7311358, and rs2053098), <i>QPRT</i> (rs13331798), and <i>SLC10A2</i> (rs188096) showed a suggestive association with LDL-cholesterol-lowering response. HDL-cholesterol-lowering responses were found to be related to <i>CYP7A1</i> gene variant (rs12542233). Seven variants, <i>SLCO1B3</i> (rs4149117, rs7311358, and rs2053098); <i>SULT1E1</i> (rs3736599 and rs3822172); and <i>ABCB11</i> (rs4148768 and rs3770603), were associated with the total cholesterol-lowering response. One variant of the <i>ABCB4</i> gene (rs2109505) was significantly associated with triglyceride-lowering response.</p><p><strong>Conclusion: </strong>This pharmacogenomic study identifies new genetic variants of DMET genes that are associated with the lipid-lowering response to statins. Genetic polymorphisms in DMET genes may impact the pharmacokinetics and lipid-lowering response to statin. The validation studies confirmations are needed in future pharmacogenomic studies.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"119-130"},"PeriodicalIF":1.9,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/23/pgpm-15-119.PMC8860396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39959843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>GABRA1</i> and <i>GABRB2</i> Polymorphisms are Associated with Propofol Susceptibility.","authors":"Youjie Zeng,&nbsp;Si Cao,&nbsp;Minghua Chen,&nbsp;Chao Fang,&nbsp;Wen Ouyang","doi":"10.2147/PGPM.S348170","DOIUrl":"https://doi.org/10.2147/PGPM.S348170","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the effect of gene polymorphisms of propofol GABA_A receptor and metabolic enzyme on drug susceptibility during the induction period of general anesthesia.</p><p><strong>Patients and methods: </strong>A total of 294 female patients aged 18-55 years, ASA I-II, who underwent hysteroscopy with intravenous general anesthesia, were included in the study. Anesthesia was induced by continuous intravenous infusion of propofol at 40 mg·kg^-1·h^-1. Infusion of propofol was ended when both the Modified Observer's Assessment of Awareness/Sedation scale (MOAA/S scale) decreased to 1 and the BIS index decreased to 60. The time when the MOAA/S scale decreased to 1 and the time when BIS index decreased to 60 was recorded to assess the susceptibility to the sedation effect. The maximum decreased percentage in mean arterial pressure (MAP) within 5 minutes was recorded to assess the susceptibility of cardiovascular response. Venous blood of each patient was collected to identify the presence of genetic variants in the <i>GABRA1, GABRA2, GABRB2, GABRB3, GABRG2, CYP2B6</i>, and <i>UGT1A9</i> genes using the Sequenom MassARRAY^® platform.</p><p><strong>Results: </strong>After receiving propofol infusion, carriers of polymorphic <i>GABRA1</i> rs4263535 G allele required significantly less time for BIS decreased to 60, while carriers of polymorphic <i>GABRB2</i> rs3816596 T allele required significantly more time for BIS decreased to 60, carriers of polymorphic <i>GABRA1</i> rs1157122 C allele and carriers of polymorphic <i>GABRB2</i> rs76774144 T allele had a significantly less change in MAP.</p><p><strong>Conclusion: </strong><i>GABRB2</i> rs3816596 and <i>GABRA1</i> rs4263535 polymorphisms are associated with susceptibility to the sedation effect of propofol. <i>GABRA1</i> rs1157122 and <i>GABRB2</i> rs76774144 polymorphisms are associated with the degree of drop in blood pressure after propofol infusion.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"105-117"},"PeriodicalIF":1.9,"publicationDate":"2022-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0d/1e/pgpm-15-105.PMC8841664.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39627018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis.","authors":"Iram Haq, Maryam Almulhem, Simone Soars, David Poulton, Malcolm Brodlie","doi":"10.2147/PGPM.S245603","DOIUrl":"10.2147/PGPM.S245603","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is an autosomal recessive genetic condition that is caused by variants in the <i>cystic fibrosis transmembrane conductance regulator</i> gene. This causes multisystem disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel at the apical surface of epithelia. Until recently, treatment was directed at managing the downstream effects in affected organs, principally improving airway clearance and treating infection in the lungs and improving malabsorption in the gastrointestinal tract. Care delivered by multidisciplinary teams has yielded incremental improvements in outcomes. However, the development of small-molecule CFTR modulator drugs over the last decade has heralded a new era of CF therapeutics. Modulators target the underlying defect and improve CFTR function. Either monotherapy or a combination of modulators is used depending on the specific genotype and class of <i>CFTR</i> disease-causing variants that an individual has. Both ivacaftor and the ivacaftor/tezacaftor/elexacaftor combination have been demonstrated to be associated with clinically very significant benefits in randomised trials and have rapidly been made available as part of standard care in many countries. CFTR modulators represent one of the best examples of precision medicine to date. They are expensive, however, and equity of access to them worldwide remains an issue. Studies and approvals are also ongoing for children under the age of 6 years for ivacaftor/tezacaftor/elexacaftor. Furthermore, no modulators are available for around 10% of the people with CF. In this review, we firstly summarise the genetics, pathophysiology and clinical problems associated with CF. We then discuss the development of CFTR modulators and key clinical trials to support their use along with other potential future therapeutic approaches.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"91-104"},"PeriodicalIF":0.0,"publicationDate":"2022-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/0d/pgpm-15-91.PMC8828078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39776049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clopidogrel Use and CYP2C19 Genotypes in Patients Undergoing Vascular Intervention Procedure: A Hospital-Based Study.","authors":"Yi-Ju Liao,&nbsp;Tzu-Hung Hsiao,&nbsp;Ching-Heng Lin,&nbsp;Chun-Sheng Hsu,&nbsp;Yen-Lin Chang,&nbsp;Yu-Wei Chen,&nbsp;Chiann-Yi Hsu,&nbsp;Yi-Ming Chen,&nbsp;Ming-Fen Wu","doi":"10.2147/PGPM.S335860","DOIUrl":"https://doi.org/10.2147/PGPM.S335860","url":null,"abstract":"<p><strong>Purpose: </strong>Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population.</p><p><strong>Patients and methods: </strong>This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed.</p><p><strong>Results: </strong>From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is *2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19-8.22).</p><p><strong>Conclusion: </strong>In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"81-89"},"PeriodicalIF":1.9,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/02/pgpm-15-81.PMC8819696.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39904259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Analysis of the Pathogenic Genes and Mutation Sites of Macrodactyly.","authors":"Jian-Feng Li,&nbsp;Guang-Lei Tian,&nbsp;Hui Pan,&nbsp;Wen-Tong Zhang,&nbsp;Da-Cun Li,&nbsp;Jing-Da Liu,&nbsp;Liang Zhao,&nbsp;Hai-Lei Li","doi":"10.2147/PGPM.S346373","DOIUrl":"https://doi.org/10.2147/PGPM.S346373","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the pathogenic genes and mutation sites of macrodactyly.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed on the pathological tissue and peripheral blood of 12 patients with macrodactyly who were operated in our hospital between June 2018 and May 2020. In order to conduct comprehensive bioinformatics analysis and screen the pathogenic genes of macrodactyly, the patients were divided into four groups: macrodactyly of finger group, macrodactyly of foot group, macrodactyly and syndactyly of finger group, and macrodactyly and syndactyly of foot group. The results of the whole-exome sequencing were verified using Sanger sequencing in order to clarify the pathogenic genes and mutation sites of macrodactyly, and immunohistochemical analysis of the protein signaling pathways encoded by the pathogenic genes was performed to observe the protein expression and further verify the mutant genes.</p><p><strong>Results: </strong>In the comprehensive bioinformatics analysis and Sanger verification of the whole-exome sequencing, the PIK3CA gene mutation was screened as the pathogenic gene of macrodactyly. The mutation sites were identified as the p.E542K (c.G1624A) and p.E545K (c.G1633A) sites of exon10 and the p.H1047R (c.A3140G) and p.G1049R (c.G3145C) sites of exon21. Among these, the p.G1049R (c.G3145C) locus was found in macrodactyly for the first time. The mutation of the PIK3CA gene was also found to lead to increased expression of serine-threonine kinase (AKT) in adipocytes in the PI3K-AKT-mTOR signaling pathway.</p><p><strong>Conclusion: </strong>Mutation of the <i>PIK3CA</i> gene leads to the enhancement of the PI3K-AKT-mTOR signaling pathway, which is the cause of macrodactyly. There is also some diversity in PIK3CA gene mutation sites.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"55-64"},"PeriodicalIF":1.9,"publicationDate":"2022-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/23/pgpm-15-55.PMC8809672.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39893713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The <i>Cyp2b6 Gene</i> Polymorphism and Phenotypic Correlation of Efavirenz-Based Combination Therapy Among the Niger Delta Ethnic Population: Implications in Modern Pharmacogenomics.","authors":"Samuel J Bunu,&nbsp;Azibanasamesa D C Owaba,&nbsp;Edebi N Vaikosen,&nbsp;Benjamin U Ebeshi","doi":"10.2147/PGPM.S345038","DOIUrl":"https://doi.org/10.2147/PGPM.S345038","url":null,"abstract":"<p><strong>Purpose: </strong>DNA polymorphism describes the difference between individuals, groups, or ethnicities, races, etc., in terms of their DNA sequences or phenotypes as relates to drug metabolism. Using predictive genotyping of drug-metabolizing genes, we can develop individuals' drug therapies that are less toxic and more effective. The main aim of the study was to evaluate genotype-phenotype-based correlation and incidence of genetic polymorphism of efavirenz blood levels among HIV/AIDS patients of the Niger Delta population.</p><p><strong>Methods: </strong>A study questionnaire was designed to obtained patients' data, blood samples were obtained, plasma was separated from the serum using a centrifuge for 5 minutes at 4000 rpm for HPLC analysis, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis was conducted using <i>Bsrl</i> endonuclease enzyme to digest the PCR amplicons. Standard efavirenz was used at 0.5, 1, 2, 4, 16 mg/L to construct a calibration curve. Data were analyzed with SPSS software using chi-square test at p-value ≤0.5 and Microsoft excel 2013, while PCR and RFLP results were obtained after 1% Agarose gel electrophoresis, respectively.</p><p><strong>Results: </strong>Phenotypic results showed that the participants had different efavirenz plasma concentrations. Six subjects (12%) had efavirenz plasma levels below 0.10 mg/L, considered ultra-rapid metabolizers (UMs), 22 (44%) 0.10 mg/L to 0.90 mg/L, classified as extensive metabolizers (EMs), 19 (38%) had 1.0 to 3.9 mg/L and were noted as intermediate metabolizers (IM), while 3 (6%) subjects showed efavirenz plasma levels from 4.0 mg/L to 6.0 mg/L, categorized as poor metabolizers (PM). RFLP results showed more than half of the population (56%) with a homozygous wild-type gene with CYP2B6*1*1 allele, 38% were CYP2B6*1*6 (heterozygous mutant) allele and 6% had homozygous mutant gene (CYP2B6*6*6 allele). Out of the 15 male subjects among the 50 patients that participated in the study, 8% were UM, 12% EM, 14% IM while no PM was observed, on the contrary, out of the 35 females participated in the study, 4% were observed as UM, 32% EM, 24% IM, while 6% were PM.</p><p><strong>Conclusion: </strong>There was no significant difference (p ≤ 0.05) between genotype and phenotype data for CYP2B6 polymorphism, among the HIV/AIDS patients that participated in this study. Genetic polymorphism of the CYP2B6 gene is prevalent among HIV/AIDs patients in the Niger Delta ethnic population on efavirenz-based HAART treatment, as the population having homozygous mutant gene or PM are >1% (6%).</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"45-54"},"PeriodicalIF":1.9,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/ea/pgpm-15-45.PMC8800862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39762882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Biological Factors Affecting the Treatment of Ticagrelor After Percutaneous Coronary Intervention in the Chinese Population.","authors":"Dongdong Yuan,&nbsp;Xiangfen Shi,&nbsp;Liping Gao,&nbsp;Gaobiao Wan,&nbsp;Hanjuan Zhang,&nbsp;Yuling Yang,&nbsp;Yujie Zhao,&nbsp;Didi Sun","doi":"10.2147/PGPM.S338287","DOIUrl":"https://doi.org/10.2147/PGPM.S338287","url":null,"abstract":"<p><strong>Background: </strong>Generally, many individual factors can affect the clinical application of drugs, of which genetic factors contribute more than 20%. Ticagrelor is a new class of receptor inhibitors receptor antagonist of P2Y12 and is used as an antiplatelet agents. But it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through pharmacogenomics research.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed in 100 patients after PCI with ticagrelor treatment. Clinical characteristics and WES of patients were used to performed genome-wide association analysis (GWAS), region-based tests of rare DNA variant to find the influencing factors of antiplatelet effect to ticagrelor and bleeding events. Co-expression, protein-protein interaction (PPI) network and pathway enrichment analysis were then used to find possible genetic mechanisms. Atlas of GWAS (https://atlas.ctglab.nl/) were used for external data validation.</p><p><strong>Results: </strong>DNAH17, PGS1 and ABCA1 as the potential variant genes are associated with the expected antiplatelet effect to ticagrelor. The affected pathways may include the synthesis and metabolism of lipoprotein cholesterol and the catabolic process of pyrimidine-containing compound (GO:0072529). Age, sex and PLT were found may be potential factors for ticagrelor bleeding events.</p><p><strong>Conclusion: </strong>We systematically identified new genetic variants and some risk factors for reduced efficacy of ticagrelor and highlighted related genes that may be involved in antiplatelet effects and bleeding event of ticagrelor. Our results enhance the understanding of the absorption and metabolic mechanisms that influence antiplatelet response to ticagrelor treatment.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03161002. First Posted: May 19, 2017. https://clinicaltrials.gov/ct2/show/study/NCT03161002.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"29-43"},"PeriodicalIF":1.9,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/3a/pgpm-15-29.PMC8786390.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39951693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}