Role of Candidate Gene Variants in Modulating the Risk and Severity of Alcoholic Hepatitis
dc.contributor.author | Beaudoin, James J. | |
dc.contributor.author | Liang, Tiebing | |
dc.contributor.author | Tang, Qing | |
dc.contributor.author | Banini, Bubu A. | |
dc.contributor.author | Shah, Vijay H. | |
dc.contributor.author | Sanyal, Arun J. | |
dc.contributor.author | Chalasani, Naga P. | |
dc.contributor.author | Gawrieh, Samer | |
dc.contributor.department | Biostatistics, School of Public Health | en_US |
dc.date.accessioned | 2023-06-05T13:27:48Z | |
dc.date.available | 2023-06-05T13:27:48Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Background: Alcoholic hepatitis (AH) is a severe and life-threatening alcohol-associated liver disease. Only a minority of heavy drinkers acquires AH and severity varies among affected individuals, suggesting a genetic basis for the susceptibility to and severity of AH. Methods: A cohort consisting of 211 patients with AH and 176 heavy drinking controls was genotyped for five variants in five candidate genes that have been associated with chronic liver diseases: rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3), rs72613567 in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), rs58542926 in transmembrane 6 superfamily member 2 (TM6SF2), rs641738 in membrane bound O-acyltransferase domain containing 7 (MBOAT7), and a copy number variant in the haptoglobin (HP) gene. We tested the effects of individual variants and the combined/interacting effects of variants on AH risk and severity. Results: We found significant associations between AH risk and the risk alleles of rs738409 (p = 0.0081) and HP (p = 0.0371), but not rs72613567 (p = 0.3132), rs58542926 (p = 0.2180), or rs641738 (p = 0.7630), after adjusting for patient's age and sex. A multiple regression model indicated that PNPLA3 rs738409:G [OR = 1.59 (95% CI: 1.15-2.22), p = 0.0055] and HP*2 [OR = 1.38 (95% CI: 1.04-1.82), p = 0.0245], when combined and adjusted for age and sex also had a large influence on AH risk among heavy drinkers. In the entire cohort, variants in PNPLA3 and HP were associated with increased total bilirubin and Model for End-stage Liver Disease (MELD) score, both measures of AH severity. The HSD17B13 rs72613567:AA allele was not found to reduce risk of AH in patients carrying the G allele of PNPLA3 rs738409 (p = 0.0921). Conclusion: PNPLA3 and HP genetic variants increase AH risk and are associated with total bilirubin and MELD score, surrogates of AH severity. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Beaudoin JJ, Liang T, Tang Q, et al. Role of candidate gene variants in modulating the risk and severity of alcoholic hepatitis. Alcohol Clin Exp Res. 2021;45(4):709-719. doi:10.1111/acer.14581 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/33492 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1111/acer.14581 | en_US |
dc.relation.journal | Alcohol Clinical & Experimental Research | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Alcoholic liver disease | en_US |
dc.subject | Genetic risk | en_US |
dc.subject | Haptoglobin | en_US |
dc.title | Role of Candidate Gene Variants in Modulating the Risk and Severity of Alcoholic Hepatitis | en_US |
dc.type | Article | en_US |