Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.
Details
Serval ID
serval:BIB_58AA7392A1FC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic Variation in HSD17B13 Reduces the Risk of Developing Cirrhosis and Hepatocellular Carcinoma in Alcohol Misusers.
Journal
Hepatology
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Publication state
Published
Issued date
07/2020
Peer-reviewed
Oui
Volume
72
Number
1
Pages
88-102
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Carriage of rs738409:G in patatin-like phospholipase domain containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with carriage of PNPLA3 rs738409:G. This study explores the risk associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC.
Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10 <sup>-6</sup> ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10 <sup>-4</sup> ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10 <sup>-26</sup> ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10 <sup>-23</sup> ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (OR <sub>allelic</sub> , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10 <sup>-4</sup> ).
Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.
Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including 1,031 with alcohol-related cirrhosis and HCC, 1,653 with alcohol-related cirrhosis without HCC, 2,588 alcohol misusers with no liver disease, and 899 healthy controls. Genetic associations with the risks for developing alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for developing both cirrhosis (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.88; P = 8.13 × 10 <sup>-6</sup> ) and HCC (OR, 0.77; 95% CI, 0.68-0.89; P = 2.27 × 10 <sup>-4</sup> ), whereas carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR, 1.70; 95% CI, 1.54-1.88; P = 1.52 × 10 <sup>-26</sup> ) and HCC (OR, 1.77; 95% CI, 1.58-1.98; P = 2.31 × 10 <sup>-23</sup> ). These associations remained significant after adjusting for age, sex, body mass index, type 2 diabetes, and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women, but the protective effect against the subsequent development of HCC was only observed in men (OR <sub>allelic</sub> , 0.75; 95% CI, 0.64-0.87; P = 1.72 × 10 <sup>-4</sup> ).
Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population.
Keywords
17-Hydroxysteroid Dehydrogenases/genetics, Aged, Aged, 80 and over, Alcoholism/complications, Carcinoma, Hepatocellular/epidemiology, Carcinoma, Hepatocellular/etiology, Carcinoma, Hepatocellular/genetics, Cohort Studies, Female, Genetic Variation, Humans, Liver Cirrhosis, Alcoholic/epidemiology, Liver Cirrhosis, Alcoholic/etiology, Liver Cirrhosis, Alcoholic/genetics, Liver Neoplasms/complications, Liver Neoplasms/epidemiology, Liver Neoplasms/etiology, Liver Neoplasms/genetics, Male, Middle Aged, Risk Assessment
Pubmed
Web of science
Create date
21/10/2019 15:30
Last modification date
06/04/2024 7:24