Genetic polymorphism of alcohol dehydrogenase 2(ADH1B) in association with alcohol consumption in Nepalese population.

Thesis Report.

ABSTRACT:

Background: Alcohol is the world's third largest risk factors for disease burden (after childhood underweight and unsafe sex), chargeable for about 4.5% Disability- Adjusted Life Years (DALY) in 2009. Liver is the main site of alcohol metabolism. The alcohol metabolizing gene, ADH1B is mostly ethnic and race dependent. Functional polymorphisms found within the genes encoding ADH1B, might lead to either increased or decreased rate of enzymatic metabolism of ingested ethanol. Thus, it's necessary to assess the single consuming alcohol in a daily basis in order to explore their genotypic influence on alcohol consumption.

Objective: The stud y was designed with the aim to observe genotypic and allele frequency in alcoholic and non-alcoholic groups and to evaluate the effects of ADH1B gene polymorphism on alcohol consumption. Methods and Methodology: A prospective cross-sectional study was conducted from July 2021 to December 2021. A total of 82 EDTA blood samples were taken from alcoholic and non-alcoholic subjects. The samples were subjected to molecular analysis for detection of ADH1B polymorphism and PCR-CTPP method was used. The ultimate products were visualized by 1.5% agarose gel electrophoresis. The resulting data was then entered into excel sheet and analyzed by SPSS v 21.0.

Results: The homozygous from ADH1B*1/*1 genotype was found to be prevalent in higher frequencies in both alcoholics and non-alcoholics groups. The frequency of ADH1B*allele was 97.55% whereas ADH1B*2 allele was found to be 2.45%. Similarly, ADH1B*1*1 genotype was found to be at a rate of 98.1%, 76.2% and 100% in individuals with aadibasi/janajati, bhraman/chhetri and madhesi ethnicities. Likewise, individuals consuming alcohol for a longer duration have ADH1B*1/*1 metabolism for such a chronic time.

Conclusion: It can be concluded from the study that the presence of ADH1B*1/*1, ADH1B*1/*2 and ADH1B*2/*genotype affects the metabolism of alcohol, consumption of alcohol and its tolerance. The presence of ADH1B*1/*1 genotype increase the tolerance alcohol and makes individual more liable to alcoholism and precede the onset of alcohol use disorders. Thus, result might indicate the presence of ADH1B*2 allele to be protective against alcoholism and its subsequent consequence.

Key Words: ADH1B polymorphism, alcohol metabolism, PRC-CTTP, genotype frequency, allele frequency.