Assessment of Glu504 Lys Genotype and Single Nucleotide Polymorphisms in Exon 12 and 13 of ALDH2 Gene in Alcoholic Liver Cirrhosis Patients in Northern Karnataka, India: A Cross-sectional Study

Abstract

Introduction: Alcoholic Liver Disease (ALD) is one of the most significant issues affecting the world today and is the principal cause of atleast 60 of the most significant forms of systemic disorders. The metabolic breakdown of alcohol into acetaldehydes is catalysed by Alcohol Dehydrogenase (ALDH). Aim: To find out the Glu504 Lys genotype and Single Nucleotide Polymorphisms (SNPs) in the exon 12 and 13 of ALDH2 gene in alcoholic liver cirrhosis patients. Materials and Methods: This cross-sectional study was conducted at the Department of General Medicine and Genetics Laboratory of the BLDE (Deemed to be University) Shri BM Patil Medical College Hospital and Research Centre (SBMPMC), Vijayapura, Karnataka, India. The study period was from January 2021 to June 2022. ALD patients were recruited. For the present study, 32 patients with ALD symptoms were recruited, and a total of 32 age- and sex-matched controls were included. Patients with existing or past co-infections with Hepatitis B or C and other causes of chronic liver disease were excluded. Blood samples were collected from all patients and subjected to genetic analysis; Polymerase Chain Reaction (PCR) products were then analysed using Sanger-based Deoxyribonucleic Acid (DNA) sequencing. Results: The mean age of all patients and controls in the present study was 44.06 and 52.09 years, respectively. Out of 32 cases, two mutations were found in exon 13: g.47794 A>T (heterozygous) and g.47854 T>G (heterozygous). These mutations occurred in patients who were younger (mean age 29.5 years) and consumed less alcohol (108 g/day) for a shorter duration (5.5 years) compared to the remaining cases. No SNPs were found in exon 12 of the ALDH2 gene. Conclusion: Mutations in the exon 13 regions of the ALDH2 gene may be responsible for early predisposition to the disease. Early genetic analysis in selected populations to identify these mutations may help prevent the occurrence of the disease. An association study of the ALDH2 gene with ALD will be conducted in larger samples, along with biochemical and other clinical investigations, to determine the association of these gene polymorphisms.

Keywords

• alcohol dehydrogenase
• alcoholic liver disease
• heterozygous mutation