Pharmacogenomics and Personalized Medicine最新文献

{"title":"Genetic Polymorphisms of Very Important Pharmacogene Variants in the Blang Population from Yunnan Province in China.","authors":"Yuliang Wang,&nbsp;Linna Peng,&nbsp;Hongyan Lu,&nbsp;Zhanhao Zhang,&nbsp;Shishi Xing,&nbsp;Dandan Li,&nbsp;Chunjuan He,&nbsp;Tianbo Jin,&nbsp;Li Wang","doi":"10.2147/PGPM.S327313","DOIUrl":"https://doi.org/10.2147/PGPM.S327313","url":null,"abstract":"<p><strong>Background: </strong>We aimed to enrich the pharmacogenomic information of a Blang population (BP) from Yunnan Province in China.</p><p><strong>Methods: </strong>We genotyped 55 very important pharmacogene (VIP) variants from the PharmGKB database and compared their genotype distribution (GD) in a BP with that of 26 populations by the <i>χ</i> ² test. The minor allele frequency (MAF) distribution of seven significantly different single-nucleotide polymorphisms (SNPs) was conducted to compare the difference between the BP and 26 other populations.</p><p><strong>Results: </strong>Compared with the GD of 55 loci in the BP, among 26 studied populations, GWD, YRI, GIH, ESN, MSL, TSI, PJL, ACB, FIN and IBS were the top-10 populations, which showed a significantly different GD >35 loci. CHB, JPT, CDX, CHS, and KHV populations had a significantly different GD <20 loci. A GD difference of 27-34 loci was found between the BP and 11 populations (LWK, CEU, ITU, STU, PUR, CLM, GBR, ASW, BEB, MXL and PEL). The GD of five loci (rs750155 (<i>SULT1A1</i>), rs4291 (<i>ACE</i>), rs1051298 (<i>SLC19A1</i>), rs1131596 (<i>SLC19A1</i>) and rs1051296 (<i>SLC19A1</i>)) were the most significantly different in the BP as compared with that of the other 26 populations. The genotype frequency of rs1800764 (<i>ACE</i>) and rs1065852 (<i>CYP2D6</i>) was different in all populations except for PEL and LWK, respectively. MAFs of rs1065852 (<i>CYP2D6</i>) and rs750155 (<i>SULT1A1</i>) showed the largest fluctuation between the BP and SAS, EUR, AFR and AMR populations.</p><p><strong>Conclusion: </strong>Our data can provide theoretical guidance for safe and efficacious personalized drug use in the Blang population.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1647-1660"},"PeriodicalIF":1.9,"publicationDate":"2021-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/25/pgpm-14-1647.PMC8691194.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39758148","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":"Interleukin-16 rs4072111 Polymorphism is Associated with the Risk of Peri-Implantitis in the Chinese Population.","authors":"Zongfei Chen,&nbsp;Guanhua Chen","doi":"10.2147/PGPM.S336857","DOIUrl":"https://doi.org/10.2147/PGPM.S336857","url":null,"abstract":"<p><strong>Purpose: </strong>Peri-implantitis (PI) is a major contributor to dental implant failure. Genetic predisposition plays an essential role in the development of PI. The purpose of this study was to investigate the correlation of <i>IL-16</i> gene single nucleotide polymorphisms (SNPs), rs11556218 and rs4072111, with PI at the gene level.</p><p><strong>Patients and methods: </strong>A total of 162 patients with PI and 162 cases with healthy implants were recruited as the case and control groups, respectively. The genotypes were analysed using direct sequencing. The genotype and allele proportion between the case and control groups were compared using the chi-square test. The periodontal status of patients carrying different genotypes was analysed, including gingival index, plaque index, calculus index, peri-implant pocket depth (PPD), and clinical attachment level (CAL).</p><p><strong>Results: </strong>The case and control groups were age- and gender-matched. In the case group, the rs4072111 CT genotype was majorly observed, and the T allele carriers showed a high PI risk. Patients with the rs4072111 CT genotype had worse periodontal status, which was reflected by the higher levels of the gingival index, plaque index, calculus index, PPD and CAL. The distribution of the rs11556218 genotype and T allele showed no significant difference between the case and control groups (<i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>The CT genotype of <i>IL-16</i> gene rs4072111 SNP can be used as a factor assessing PI risk. Therefore, <i>IL-16</i> genetic variation may be related to PI susceptibility in the Chinese Han population.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1629-1635"},"PeriodicalIF":1.9,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/a2/pgpm-14-1629.PMC8686223.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39625795","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 Landscape of Clinical Implementation of Pharmacogenetic Testing in Central China: A Single-Center Study.","authors":"Jingmin Zhang,&nbsp;Guangzhao Qi,&nbsp;Chao Han,&nbsp;Yubing Zhou,&nbsp;Yongjie Yang,&nbsp;Xinru Wang,&nbsp;Suna Liu,&nbsp;Xiaojian Zhang","doi":"10.2147/PGPM.S338198","DOIUrl":"https://doi.org/10.2147/PGPM.S338198","url":null,"abstract":"<p><strong>Purpose: </strong>Pharmacogenetic testing is recognized as the major method for the individualized pharmacotherapy in clinical pharmacy practice, but information about the clinical implementation of pharmacogenetic testing in China is limited. The present study aimed to determine the situation of clinical implementation for pharmacogenetic testing in central China.</p><p><strong>Methods: </strong>The study is conducted in the department of clinical pharmacy in The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. We collected and analyzed pharmacogenetic testing results from November 1, 2013 to November 2, 2018 in our hospital, which were checked in the electronic medical record system. The main outcome measures were the number and type of pharmacogenetic testing across five years.</p><p><strong>Results: </strong>A total of 47,265 (56.9% male, mean age = 51.5 years) pharmacogenetic testing results were obtained with an average annual rate of growth of 63.0% across five years. A 50.2% (23,748/47,265) of all the pharmacogenetic testing results were for the determination of cytochrome P450 2C19 (<i>CYP2C19</i>) *2, *3 genotypes, and 41.7% were for the methylene tetrahydrofolate reductase (<i>MTHFR</i>) C677T genotype. The number of departments performing the pharmacogenetic testing was 35, 63, 55, 52, 52 and 39 for 2013-2018, respectively, and the main top five departments were cardiology, psychiatry, ICU, cardiac surgery and intervention.</p><p><strong>Conclusion: </strong>Clinical implementation of pharmacogenetic testing in China is growing rapidly, but the types and implementing departments of pharmacogenetic testing were limited. Our present study reported the real-world implementation modality of pharmacogenomic tests in China. It will help us to understand the testing of pharmacogenetics in China in order to promote the rational development of pharmacogenetics.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1619-1628"},"PeriodicalIF":1.9,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/32/pgpm-14-1619.PMC8684419.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39745838","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":"Ethnic Diversity of DPD Activity and the <i>DPYD</i> Gene: Review of the Literature.","authors":"Cassandra White,&nbsp;Rodney J Scott,&nbsp;Christine Paul,&nbsp;Andrew Ziolkowski,&nbsp;David Mossman,&nbsp;Stephen Ackland","doi":"10.2147/PGPM.S337147","DOIUrl":"https://doi.org/10.2147/PGPM.S337147","url":null,"abstract":"<p><p>Pharmacogenomic screening can identify patients with gene variants that predispose them to the development of severe toxicity from fluoropyrimidine (FP) chemotherapy. Deficiency of the critical metabolic enzyme dihydropyrimidine dehydrogenase (DPD) leads to excessive toxicity on exposure to fluoropyrimidine chemotherapy. This can result in hospitalisation, intensive care admissions and even death. Upfront screening of the gene that encodes for DPD (<i>DPYD</i>) has recently been implemented in regions throughout Europe and the United Kingdom. Current screening evaluates <i>DPYD</i> variants that are well described within Caucasian patient populations and provides genotyped-guided dose adjustment recommendations based upon the presence of these variants. This article reviews the differences in <i>DPYD</i> gene variants within non-Caucasian populations compared to Caucasian populations, with regard to the implications for clinical tolerance of fluoropyrimidine chemotherapies and genotype guided dose adjustment guidelines.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1603-1617"},"PeriodicalIF":1.9,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/b4/pgpm-14-1603.PMC8668257.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39733802","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":"FTO Gene Polymorphisms Contribute to the Predisposition and Radiotherapy Efficiency of Nasopharyngeal Carcinoma [Retraction].","authors":"","doi":"10.2147/PGPM.S352184","DOIUrl":"https://doi.org/10.2147/PGPM.S352184","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/PGPM.S325895.].</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1601-1602"},"PeriodicalIF":1.9,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/69/d5/pgpm-14-1601.PMC8667606.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39733801","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 a Novel VPS13B Mutation in a Chinese Patient with Cohen Syndrome by Whole-Exome Sequencing.","authors":"Xiaoyun Hu,&nbsp;Tao Huang,&nbsp;Yun Liu,&nbsp;Lina Zhang,&nbsp;Li Zhu,&nbsp;Xiaohong Peng,&nbsp;Sufang Zhang","doi":"10.2147/PGPM.S327252","DOIUrl":"https://doi.org/10.2147/PGPM.S327252","url":null,"abstract":"<p><strong>Objective: </strong>The present study aims to investigate the clinical features and diagnostic characteristics of children with Cohen syndrome caused by the vacuolar protein sorting 13 homolog B (VPS13B) gene mutation and to review the relevant literature to provide a reference for genetic counseling and the diagnosis of Cohen syndrome.</p><p><strong>Methods: </strong>The clinical data and molecular genetic test results of a child with Cohen syndrome were retrospectively analyzed and a review of the relevant literature was conducted.</p><p><strong>Results: </strong>A two-year-and-four-month-old boy was referred to the hospital for recurrent fever and shortness of breath. On physical examination, the boy was found to have growth retardation, thick bushy hair, microcephaly, hypertelorism, down-slanting palpebral fissures, and hypotonia. Genetic testing was performed, and the results suggested the presence of exon 20-32 heterozygous deletion and c.8275 delC (p.R2759 fs*18) heterozygous variant on the VPS13B gene from phenotypically normal parents. These two mutation loci have not been reported in the literature, and they were predicted by relevant software to be pathogenic variants.</p><p><strong>Conclusion: </strong>We identified two novel variants in the VPS13B gene (exon 20-32 heterozygous deletion and c.8275 delC heterozygous variant) in a boy with Cohen syndrome, thus extending the spectrum of VPS13B gene variants in patients with Cohen syndrome.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1583-1589"},"PeriodicalIF":1.9,"publicationDate":"2021-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/11/pgpm-14-1583.PMC8657012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39808200","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":"Genetic Variant of PP2A Subunit Gene Confers an Increased Risk of Primary Liver Cancer in Chinese.","authors":"Youxin Wang,&nbsp;Qiuyue Huang,&nbsp;Xinglei Huang,&nbsp;Huiliu Zhao,&nbsp;Bin Guan,&nbsp;Kechen Ban,&nbsp;Xuefeng Zhu,&nbsp;Zhixing Ma,&nbsp;Yanmei Tang,&nbsp;Zhaohui Su,&nbsp;Qingqing Nong","doi":"10.2147/PGPM.S335555","DOIUrl":"https://doi.org/10.2147/PGPM.S335555","url":null,"abstract":"<p><strong>Background: </strong>Protein phosphatase 2A (PP2A, a serine/threonine phosphatase) is frequently inactivated in many types of cancer, including primary liver cancer (PLC). Genetic variations in PP2A subunits have been reported to be associated with the risk of many types of cancer but rarely in PLC. This study aims to assess the association between functional polymorphisms of PP2A subunit genes and the risk of PLC in Chinese.</p><p><strong>Methods: </strong>In a case-control study with a total of 541 PLC patients and 547 controls in Guangxi province of Southern China, we genotyped six putatively functional polymorphisms (rs10421191G>A, rs11453459del>insG, rs1560092T>G, rs7840855C>T, rs1255722G>A and rs10151527A>C) of three PP2A subunit genes (PPP2R1A, PPP2R2A and PPP2R5E) using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform.</p><p><strong>Results: </strong>The rs11453459insG variant genotypes (ins/ins+del/ins) of PPP2R1A were found to be significantly associated with an increased risk of PLC compared with the del/del genotype (adjusted OR = 1.290, 95% CI = 1.009-1.650), and the number of insert G allele worked in a dose-dependent manner (<i>P</i> _trend= 0.007). The stratified analysis showed that the effects of rs11453459insG variant genotypes were more evident in the subgroup who drink pond-ditch water (adjusted OR = 3.051, 95% CI = 1.264-7.364) than those never drink (<i>P</i> = 0.041). The carriers of rs11453459 del/ins genotype had a significantly lower level of PPP2R1A mRNA expression in liver cancer tissues than those of the del/del genotype (<i>P</i> = 0.021). Furthermore, we used microcystin-LR, a carcinogen presents in the pond-ditch water, to treat human peripheral blood mononuclear cells and found that the cells from carriers of rs11453459insG variant genotypes induced more DNA oxidative damages than those from the del/del genotype carriers (<i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>These findings suggest that the PPP2R1A rs11453459del>insG polymorphism is associated with an increased risk of PLC, especially for persons with a history of drinking pond-ditch water. This insertion/deletion polymorphism may be a susceptible biomarker for PLC in Chinese.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1565-1574"},"PeriodicalIF":1.9,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/62/pgpm-14-1565.PMC8654694.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39719236","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":"Development and Validation of a Prognostic N6-Methyladenosine-Related Immune Gene Signature for Lung Adenocarcinoma.","authors":"Lemeng Zhang,&nbsp;Yongzhong Luo,&nbsp;Tianli Cheng,&nbsp;Jianhua Chen,&nbsp;Hua Yang,&nbsp;Xiaoping Wen,&nbsp;Zhou Jiang,&nbsp;Haitao Li,&nbsp;Changqie Pan","doi":"10.2147/PGPM.S332683","DOIUrl":"https://doi.org/10.2147/PGPM.S332683","url":null,"abstract":"<p><strong>Purpose: </strong>The prognostic value of an N6-methyladenosine (m6A) methylation-related immune gene signature for lung adenocarcinoma (LUAD) was investigated.</p><p><strong>Patients and methods: </strong>Gene expression and clinical phenotype data of LUAD patients were downloaded from The Cancer Genome Atlas database. A list of immune-related genes was retrieved from the InnateDB database. Correlation analysis, survival analysis, and univariate and multivariate Cox regression analyses were performed. After allocating patients into a high-risk or a low-risk group, the corresponding survival rates, immune microenvironment, expression of immune checkpoint genes, and modulation of Kyoto Encyclopedia of Genes and Genomes pathways were examined. Finally, the expression levels of prognostic biomarkers were assessed in the GSE126044 dataset.</p><p><strong>Results: </strong>Seven m6A-related immune prognostic genes were identified. High expression of <i>PSMD10P1, DIDO1, ABCA5</i>, and <i>CIITA</i> was associated with high survival rates, while that of <i>PRC1, ZWILCH</i>, and <i>ANLN</i> was associated with low survival rates. The high- and low-risk groups showed significant differences in terms of the abundance of six tumor-infiltrating immune cell types and expression of 12 immune checkpoint genes. The risk group acted as an independent prognostic factor (hazard ratio = 0.398, 95% confidence interval = 0.217-0.729, P = 0.003). Finally, the developed nomogram could predict most efficiently the 1-, 2-, and 3-year survival probability of LUAD patients with a C-index of 0.833.</p><p><strong>Conclusion: </strong>A seven-gene risk signature, associated with the immune microenvironment in LUAD, showed independent prognostic value.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1549-1563"},"PeriodicalIF":1.9,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/e2/pgpm-14-1549.PMC8643173.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39790468","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":"Genetic Polymorphism of Drug Metabolic Gene <i>CYPs, VKORC1, NAT2, DPYD</i> and <i>CHST3</i> of Five Ethnic Minorities in Heilongjiang Province, Northeast China.","authors":"Tingting Zhang,&nbsp;Qiuyan Li,&nbsp;Bonan Dong,&nbsp;Xiao Liang,&nbsp;Mansha Jia,&nbsp;Jing Bai,&nbsp;Jingcui Yu,&nbsp;Songbin Fu","doi":"10.2147/PGPM.S339854","DOIUrl":"https://doi.org/10.2147/PGPM.S339854","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic variability in genes encoding drug-metabolizing enzymes may contribute to the heterogeneity of drug responses in different populations. Extensive research in pharmacogenomics in major populations around the world provides us with a great deal of information about drug-related genetic polymorphisms.</p><p><strong>Objective: </strong>The purpose of this study was to detect the genetic variation of drug-metabolism-related genes in the five ethnic minorities Daur, Hezhen, Ewenki, Mongolian and Manchu in China, and to analyze the distribution differences among ethnic groups.</p><p><strong>Methods: </strong>We genotyped 32 SNPs of drug metabolism genes in 882 healthy Chinese volunteers from five ethnic groups. The genotype frequency and allele frequency of the five ethnic groups were calculated, and the different variants among the five ethnic groups were compared by chi-square test. Genetic parameters were analyzed using Popgene software. The genetic structure of five ethnic minorities was analyzed by principal component analysis, and compared with 26 populations.</p><p><strong>Results: </strong>We found that SNPs of genes related to drug metabolism existed diversity in different populations. Among them, rs8192766 and rs9419082 in <i>CYP2E1</i> showed statistical differences between Daur and Manchu, and <i>NAT2</i> rs1801280 showed statistical differences between Hezhen and Mongolian. In addition, the five populations we studied had the smallest differences with EAS populations. There was haplotype diversity in <i>CHST3, VKORC1, CYP1A2</i> and <i>CYP2E1</i> genes in the five ethnic minorities, and these haplotype polymorphisms were related to the use of corresponding drug doses. Cluster analysis shows that the five ethnic minorities in Heilongjiang Province are clustered together with the EAS populations.</p><p><strong>Conclusion: </strong>These results suggest that understanding the diversity of drug-related genetic markers is critical for individualized drug gene therapy programs in ethnic minorities in China as well as in populations highly mixed with these ethnic groups.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1537-1547"},"PeriodicalIF":1.9,"publicationDate":"2021-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/78/pgpm-14-1537.PMC8643223.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39790467","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":"A Missense Variant in Granulysin is Associated with the Efficacy of Pegylated-Interferon-Alpha Therapy in Chinese Patients with HBeAg-Positive Chronic Hepatitis B.","authors":"Jing Li,&nbsp;Haitao Chen,&nbsp;Jiaxuan Chen,&nbsp;Bin Zhou,&nbsp;Jinlin Hou,&nbsp;De-Ke Jiang","doi":"10.2147/PGPM.S337962","DOIUrl":"https://doi.org/10.2147/PGPM.S337962","url":null,"abstract":"<p><strong>Purpose: </strong>Granulysin (GNLY) is a cytotoxic granule that has been reported to have various antimicrobial activities. We evaluated the association between a missense variant in <i>GNLY</i> (rs11127) and treatment efficacy of pegylated interferon-alpha (PegIFNα) or nucleos(t)ide analogs (NUCs) in patients with chronic hepatitis B (CHB).</p><p><strong>Patients and methods: </strong>We included a total of 1823 patients with hepatitis B e antigen (HBeAg)-positive CHB (954 patients treated with PegIFNα and 869 patients treated with NUCs) in four Phase IV multicenter randomized controlled trials. The association of the <i>GNLY</i> rs11127 genotype with the combined response (CR), defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA level <2000 IU/mL was evaluated. A polygenic score (PGS) was constructed to evaluate the cumulative effect of multiple single-nucleotide polymorphisms (SNPs), including rs11127 and several other SNPs, <i>STAT4</i> rs7574865, <i>CFB</i> rs12614, and <i>CD55</i> rs28371597, which were reported to be associated with CR.</p><p><strong>Results: </strong><i>GNLY</i> rs11127 was significantly associated with CR in patients treated with PegIFNα. The CR rate in patients with the rs11127 CC genotype was higher than that with the CT or TT genotype (40.98% vs 30.34% or 27.09%, <i>P</i> = 0.003). Furthermore, a PGS integrating <i>GNLY</i> rs11127 and three other SNPs was significantly associated with CR in PegIFNα-treated patients (<i>P</i> < 0.001). However, no significant correlation was found between <i>GNLY</i> rs11127 and CR in NUCs-treated patients.</p><p><strong>Conclusion: </strong><i>GNLY</i> rs11127 is an independent biomarker for predicting the response to PegIFNα therapy in HBeAg-positive CHB patients. Furthermore, the PGS, including <i>GNLY</i> rs11127, provides new insights for individualized treatment in clinical practice.</p>","PeriodicalId":509088,"journal":{"name":"Pharmacogenomics and Personalized Medicine","volume":" ","pages":"1505-1515"},"PeriodicalIF":1.9,"publicationDate":"2021-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/ea/pgpm-14-1505.PMC8627316.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39769046","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}