{"title":"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","authors":"Aki J Käräjämäki, Janne Hukkanen, 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":"{\"title\":\"Pregnane X receptor gene variant rs7643645 and total mortality in subjects with nonalcoholic fatty liver disease.\",\"authors\":\"Aki J Käräjämäki, Janne Hukkanen, 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}","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}
Pregnane X receptor gene variant rs7643645 and total mortality in subjects with nonalcoholic fatty liver disease.
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.
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.