Association of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with Alcohol abuse and Alcoholic Cirrhosis in People Living in Northeast Vietnam

Abstract

Objective: Alcohol abuse can cause developing cirrhosis, even liver cancer. Several single nucleotide polymorphisms (SNPs) of ADH1B , ADH1C , and ALDH2 genes have been reported to be associated with alcohol abuse and alcoholic cirrhosis (ALC). This study investigated the association between three SNPs of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with alcohol abuse and ALC in people living in the Northeast region of Vietnam. Methods: 306 male participants were recruited including 206 alcoholics (106 ALC, 100 without ALC) and 100 healthy non-alcoholics. Clinical characteristics were collected by clinicians. Genotypes were identified by Sanger sequencing. Chi-Square (χ2) and Fisher-exact tests were used to assess the differences in age and clinical characteristics, Child-Pugh score, frequencies of alleles and genotypes. Result: Our data showed that the frequency of ALDH2 *1 was significantly higher in alcoholics (88.59%) and ALC groups (93.40%) than that of healthy non-alcoholics (78.50%) with p=0.0009 and non-ALC group (83.50%) with p=0.002, respectively. We detected opposite results when examined ALDH2 *2. Frequency of combined genotypes with high acetaldehyde accumulation were significantly lower in alcoholics and ALC group than those of control groups with p=0.005 and p=0.008, respectively. Meanwhile, the proportion of combined genotypes with non-acetaldehyde accumulation were significantly two times higher in the ALC group (19.98%) than those of the non-ALC group (8%) with p=0.035. These combined genotypes showed a decreasing trend in the Child-Pugh score from likely phenotype causing risk for non-acetaldehyde accumulation to high acetaldehyde accumulation. Conclusion: The ALDH2 *1 allele was found as a risk factor for alcohol abuse and ALC, and combined genotypes of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with non-acetaldehyde accumulation increase ALC risk. In contrast, ALDH2 *2 and the genotype combinations related to high acetaldehyde accumulation were protective factors against alcohol abuse and ALC.

Implementing Core Genes and an Omnigenic Model for Behaviour Traits Prediction in Genomics

“…Risk of alcohol dependence, while being a complex trait, can be influenced by only two known genome variants that significantly impact its risk. Such variants are also interesting due to their distinct frequencies in East Asia compared to other populations worldwide, leading to a lower risk of alcohol dependence in East Asia [ 30 , 31 ].…”

“…Genetic diversity and unique evolutionary histories among different populations can contribute to substantial variation in the frequency of these variants without altering the effect of the specific variant. A clear example of this is the distinct frequencies of previously described variants associated with alcohol dependence, such as rs1229984 in the ADH1B gene and rs671 in the ALDH2 gene, observed in East Asia compared to other populations worldwide [ 30 , 31 ].…”