Pregnane X receptor gene variant rs7643645 and total mortality in subjects with nonalcoholic fatty liver disease.

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pharmacogenetics and genomics Pub Date : 2023-02-01 DOI:10.1097/FPC.0000000000000489
Aki J Käräjämäki, Janne Hukkanen, Olavi Ukkola
{"title":"Pregnane X receptor gene variant rs7643645 and total mortality in subjects with nonalcoholic fatty liver disease.","authors":"Aki J Käräjämäki,&nbsp;Janne Hukkanen,&nbsp;Olavi Ukkola","doi":"10.1097/FPC.0000000000000489","DOIUrl":null,"url":null,"abstract":"<p><p>Pregnane X receptor (PXR) gene variants rs7643645 and rs2461823 are reported to associate with clinically and histologically more severe liver injury in nonalcoholic fatty liver disease (NAFLD). It is known that the more progressive the NAFLD, the higher the hepatic and extra-hepatic mortality and morbidity. Thus, we investigated the total mortality in Finnish middle-aged ultrasonographically verified NAFLD patients with PXR rs7643645 AA/AG ( n  = 217) or GG ( n  = 27) variants and rs2461823 CC/CT ( n  = 215) or TT ( n  = 27) variants. In up to 30 years of follow-up, PXR rs7643645 GG subjects were at an increased risk of total mortality compared with AA/AG subjects, 1.676 (1.014-2.772), P  = 0.044. The statistically significant difference prevailed after multiple adjustments for potentially confounding factors, RR, 2.024 (1.191-3.440), P  = 0.009. In the subjects without NAFLD ( n  = 731), the mortality risk was not associated with rs7643645 variants, 1.051 (0.708-1.560; P  = 0.804). There was no difference in the total mortality between the PXR rs2461823 variant subgroups, 1.141 (0.663-1.962; P  = 0.634). As the rs7643645 G variant disrupts a putative hepatocyte nuclear factor 4α binding site located in the PXR gene promoter and is associated with lower hepatic expression of PXR and its target genes, our result suggests that genetic disruption of xenobiotic metabolism increases mortality in subjects with NAFLD. Further studies are needed to confirm the results of the present study.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"33 2","pages":"35-39"},"PeriodicalIF":1.7000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenetics and genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FPC.0000000000000489","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 1

Abstract

Pregnane X receptor (PXR) gene variants rs7643645 and rs2461823 are reported to associate with clinically and histologically more severe liver injury in nonalcoholic fatty liver disease (NAFLD). It is known that the more progressive the NAFLD, the higher the hepatic and extra-hepatic mortality and morbidity. Thus, we investigated the total mortality in Finnish middle-aged ultrasonographically verified NAFLD patients with PXR rs7643645 AA/AG ( n  = 217) or GG ( n  = 27) variants and rs2461823 CC/CT ( n  = 215) or TT ( n  = 27) variants. In up to 30 years of follow-up, PXR rs7643645 GG subjects were at an increased risk of total mortality compared with AA/AG subjects, 1.676 (1.014-2.772), P  = 0.044. The statistically significant difference prevailed after multiple adjustments for potentially confounding factors, RR, 2.024 (1.191-3.440), P  = 0.009. In the subjects without NAFLD ( n  = 731), the mortality risk was not associated with rs7643645 variants, 1.051 (0.708-1.560; P  = 0.804). There was no difference in the total mortality between the PXR rs2461823 variant subgroups, 1.141 (0.663-1.962; P  = 0.634). As the rs7643645 G variant disrupts a putative hepatocyte nuclear factor 4α binding site located in the PXR gene promoter and is associated with lower hepatic expression of PXR and its target genes, our result suggests that genetic disruption of xenobiotic metabolism increases mortality in subjects with NAFLD. Further studies are needed to confirm the results of the present study.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
妊娠X受体基因变异rs7643645与非酒精性脂肪肝患者的总死亡率
据报道,妊娠素X受体(PXR)基因变异rs7643645和rs2461823与非酒精性脂肪性肝病(NAFLD)的临床和组织学上更严重的肝损伤相关。众所周知,NAFLD越进展,肝脏和肝外死亡率和发病率越高。因此,我们研究了超声检查证实的芬兰中年NAFLD患者PXR rs7643645 AA/AG (n = 217)或GG (n = 27)变异和rs2461823 CC/CT (n = 215)或TT (n = 27)变异的总死亡率。在长达30年的随访中,与AA/AG受试者相比,PXR rs7643645 GG受试者的总死亡率风险增加,为1.676 (1.014-2.772),P = 0.044。对潜在混杂因素进行多重校正后,差异有统计学意义,RR为2.024 (1.191 ~ 3.440),P = 0.009。在没有NAFLD的受试者中(n = 731),死亡风险与rs7643645变异无关,为1.051 (0.708-1.560;P = 0.804)。PXR rs2461823变异亚组间的总死亡率无差异,分别为1.141 (0.663-1.962;P = 0.634)。由于rs7643645 G变异破坏了PXR基因启动子中一个假定的肝细胞核因子4α结合位点,并与PXR及其靶基因在肝脏中的低表达有关,我们的研究结果表明,外源代谢的遗传破坏增加了NAFLD患者的死亡率。需要进一步的研究来证实本研究的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
期刊最新文献
Polygenic risk score for drug-induced long QT syndrome: independent validation in a real-world patient cohort. The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation. Updated analysis of the pharmacogenomics of pediatric bronchodilator response. Association of ADH1B and ALDH2 genotypes with the risk of lung adenocarcinoma. Differential distribution of NAT2 polymorphisms and NAT2 acetylator phenotypes among indigenous populations of the Brazilian Amazon.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1