{"title":"HLA-DQA1*05和上游PPARGC1B变异与日本克罗恩病患者的英夫利昔单抗持久性相关。","authors":"Fumiko Shimoda, Takeo Naito, Yoichi Kakuta, Yosuke Kawai, Katsushi Tokunaga, NCBN Controls WGS Consortium, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune","doi":"10.1038/s41397-023-00312-z","DOIUrl":null,"url":null,"abstract":"Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E−9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E−5 and 5.80E−4, respectively).","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-023-00312-z.pdf","citationCount":"0","resultStr":"{\"title\":\"HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients\",\"authors\":\"Fumiko Shimoda, Takeo Naito, Yoichi Kakuta, Yosuke Kawai, Katsushi Tokunaga, NCBN Controls WGS Consortium, Yusuke Shimoyama, Rintaro Moroi, Hisashi Shiga, Masao Nagasaki, Yoshitaka Kinouchi, Atsushi Masamune\",\"doi\":\"10.1038/s41397-023-00312-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E−9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E−5 and 5.80E−4, respectively).\",\"PeriodicalId\":54624,\"journal\":{\"name\":\"Pharmacogenomics Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2023-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41397-023-00312-z.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41397-023-00312-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics Journal","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41397-023-00312-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients
Recently, the HLA-DQA1*05 (rs2097432) genetic variation has been reported to be linked to early infliximab (IFX) treatment failure in the Caucasian Crohn’s disease (CD) population, but that evidence is scarce in the Asian population. This study aimed to investigate the relationship between rs2097432 and the cumulative discontinuation-free time of IFX (IFX persistence) in 189 Japanese biologics-naive CD patients. We also performed a genome-wide association study (GWAS) to discover novel genetic predictors for IFX persistence. The C allele of rs2097432 significantly increased the risk of early discontinuation of IFX [Hazard ratio (HR) = 2.23 and P-value = 0.026]. In GWAS, one locus tagged by rs73277969, located upstream of PPARGC1B which attenuates macrophage-mediated inflammation, reached genome-wide significance (HR = 6.04 and P-value = 7.93E−9). Pathway analysis suggested association of signaling by PDGF and FCGR activation signaling with IFX persistence (P-value = 8.56E−5 and 5.80E−4, respectively).
期刊介绍:
The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications.
Key areas of coverage include:
Personalized medicine
Effects of genetic variability on drug toxicity and efficacy
Identification and functional characterization of polymorphisms relevant to drug action
Pharmacodynamic and pharmacokinetic variations and drug efficacy
Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics
Clinical applications of genomic science
Identification of novel genomic targets for drug development
Potential benefits of pharmacogenomics.