Genetic polymorphism of HLA-DRA and alcohol consumption affect hepatitis development in the Korean population

Background: Hepatitis is an inflammation of the liver that has several potential causes; however, the genetic association has recently begun to be studied.

Objectives: Human leukocyte antigen (HLA) is an essential component of the immune response, and in this study, we conducted a correlation analysis to determine whether genetic polymorphisms of HLA and drinking habits affect hepatitis development.

Methods: Genetic polymorphisms of HLA were investigated using Korean genomic and epidemiological data. A gene association study was performed using PLINK version 1.07. Other statistical analyses and multivariate logistic regression analyses were performed using PASW Statistics version 18.0.

Results: Thirteen single nucleotide polymorphisms (SNPs) in HLA-DRA showed significant statistical correlations with hepatitis. In particular, rs9268645 showed the highest statistical association with hepatitis (P = 3.97 × 10^-5, odds ratio [OR] = 0.72, 95% confidence interval [CI] = 0.61-0.84). In multivariate logistic regression analysis, when considering only genetic factors, the A allele of rs9268644 showed a reduced hepatitis OR of approximately 0.52-fold. However, the group carrying the minor A allele (AA + AC) with alcohol consumption had an approximately 1.58-fold OR of hepatitis compared to that of the group carrying the same allele with no alcohol consumption. This implies that the A allele of rs9268644 has a protective effect on hepatitis by genetic factors and shows sensitivity to alcohol.

Conclusions: Our results showed that hepatitis is influenced by both genetic and external factors (drinking habits), which can provide new guidelines for the prevention or treatment of hepatitis.