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。

IF 2.9 3区医学 Q2 GENETICS & HEREDITY

Pharmacogenomics Journal Pub Date : 2023-07-17 DOI:10.1038/s41397-023-00312-z

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

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引用次数: 0

摘要

最近，HLA-DQA1*05 (rs2097432)遗传变异被报道与高加索克罗恩病(CD)人群的早期英夫利昔单抗(IFX)治疗失败有关，但这一证据在亚洲人群中很少。本研究旨在探讨189名日本生物制剂初治CD患者rs2097432与IFX累积无停药时间(IFX持续时间)的关系。我们还进行了一项全基因组关联研究(GWAS)，以发现IFX持久性的新的遗传预测因子。rs2097432的C等位基因显著增加IFX早期停药的风险[HR = 2.23, p值= 0.026]。在GWAS中，位于PPARGC1B上游的一个rs73277969标记的位点具有全基因组意义(HR = 6.04, p值= 7.93E-9)，该位点可减轻巨噬细胞介导的炎症。通路分析表明PDGF和FCGR激活信号与IFX持续性相关(p值分别为8.56E-5和5.80E-4)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

HLA-DQA1*05 and upstream variants of PPARGC1B are associated with infliximab persistence in Japanese Crohn’s disease patients

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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).

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

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.