Genetic variant rs72613567 of HSD17B13 gene reduces alcohol‐related liver disease risk in Chinese Han population

Abstract

Background & Aims Recently, the variant rs72613567:TA in the 17‐beta‐hydroxysteroid dehydrogenase 13 (HSD17B13) has been associated with reduced levels of ALT and AST and a reduced risk of alcohol‐related liver disease (ALD) in the European population. Therefore, the aim of this study was to investigate the association between the polymorphisms of HSD17B13 and ALD, liver serum markers and patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) p.I148M in the Chinese Han population. Methods A case‐control study was performed from five centres and included 769 ALD patients and 767 healthy controls. Two SNPs (rs72613567 and rs6834314) in HSD17B13 were genotyped using the Sequenom MassArray system and allele association analysis was performed using PLINK 1.90 software. Results HSD17B13 rs72613567:TA allele was associated with a reduced risk of ALD by 19% (95% confidence interval [CI]: 0.05‐0.31, P = .01), uniformly, the G allele in the rs6834314 reduced the risk of ALD by 19% (95% CI: 0.05‐0.31, P = 8.28 × 10−3). And the genotypes of two SNPs were associated with reducing the risk of ALD in three genetic model analysis. In addition, we found that TA allele was associated with lower levels of serum ALT, AST and GGT (P = .005, .007 and .02, respectively), higher level of serum ALB (P = .02), but not associated with ALP. In this cohort, the interaction between HSD17B13 rs72613567 and the steatogenic allele PNPLA3 rs738409 was not validated. Conclusion The present study revealed that HSD17B13 rs72613567 was significantly associated with a reduced risk of ALD in Chinese Han population.

HSD17B13: A Potential Therapeutic Target for NAFLD

“…Consistently, the genetic variant rs72613567 of the HSD17B13 gene was also found to reduce alcohol-related liver disease (ALD) risk in the Chinese Han population. In a case-control study including 769 ALD patients and 767 healthy controls, the HSD17B13 rs72613567:TA allele was associated with a decreased risk of ALD by 19% (Chen et al, 2020). Furthermore, a combination of another HSD17B13:rs68343143 variant and two other genetic variants (PNPLA3:rs738409 and TM6SF2:rs10401969) can predict the development of alcohol-related cirrhosis in heavy drinkers (Whitfield et al, 2021).…”

Alcohol-Related Liver Disease: Basic Mechanisms and Clinical Perspectives

“…The rs72613567 T > A variant results in shortened protein production and reduced enzymatic activity, which is associated with both ALD and NAFLD progression to cirrhosis or HCC, and decreased liver enzyme levels [44]. These findings were validated in two recent large cohort studies in different ethnic groups with alcohol use, suggesting the therapeutic potential of HSD17B13 in the future [65,66].…”

Differences in complications between hepatitis B-related cirrhosis and alcohol-related cirrhosis

“…Chronic HBV infection was defined based on serum hepatitis B surface antigen positivity for >6 months. Alcohol-related cirrhosis was defined as cirrhosis together with alcoholism (alcohol consumption ≥20 g/day in women and ≥40 g/day in men for >5 years) in the absence of other liver diseases [ 14 ]. ACLF was defined as INR ≥1.5 and serum bilirubin ≥5 mg/dL, complicated by encephalopathy and/or ascites within 4 weeks, in cirrhotic patients [ 15 ].…”