Genetic profiles of single nucleotide polymorphisms in alcohol metabolizing enzymes in the Ugandan population

Abstract

The pathway for alcohol (ethanol) metabolism in the body is catalyzed by alcohol dehydrogenase enzymes (ADHs), catalase (CAT) and CYP2E1 to generate acetaldehyde, which is metabolized by aldehyde dehydrogenase enzymes (ALDHs). Genetic polymorphisms that lead to varying elimination rates of alcohol have been reported in these four enzymes. Frequencies of these polymorphisms have also been reported to be different in various populations across the world. The aim of this study was to determine the genotype and allele frequencies of single nucleotide polymorphisms in genes that encode the four alcohol metabolizing enzymes in 250 healthy members of the Ugandan population. The allele specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism genotyping techniques were applied. The ADH1B rs1229984 SNP had a genotype frequency of 99.6% G/G and 0.4% G/A while the allele frequency was 99.8% G and 0.2% A. ADH1B rs2066702 had 65.6% C/C, 32.4% C/T and 2.0% T/T genotype frequencies as well as 81.8% C and 18.2% T allele frequencies. For ADH1C, the ADH1C rs1693482 SNP had genotype frequencies of 80.8% G/G, 17.2% G/A and 2.0% A/A as well as allele frequencies of 89.4% G and 10.6% A. The ADH1C rs698 SNP had genotype frequencies of 1.2% A/A, 96.8% A/G and 2.0% G/G together with allele frequencies of 49.6% A and 50.4% G. The ALDH2 rs671 polymorphism showed 100% G/G genotype and 100% G-allele. In cytochrome P450, the CYP2E1 rs72559710 polymorphism showed 100% G/G genotype and 100% G-allele frequency whereas the CYP2E1 rs55897648 polymorphism showed 100% G/A genotype with 50% G and 50% A allele frequencies. The CYP2E1 rs3813867 SNP yielded 92.0% G/G and 8.0% G/C genotype with 96.0% G and 4.0% C allele frequencies while the CYP2E1 rs6413432 SNP yielded 64.0% T/A and 36.0% A/A genotype with 32.0% T and 68.0% A allele frequencies. The CYP2E1 rs6413420 SNP produced 88.0% G/G and 11.2% G/T genotypic frequencies with 94.4% G and 5.6% T allelic frequencies. For the catalase gene, the CAT rs794316 polymorphism had 24.0% A/A, 50.4% A/T and 25.6% T/T genotype frequencies with 49.2% A and 50.8% T allele frequencies. The CAT rs1001179 SNP showed 98.4% C/T and 1.6% T/T genotypic frequencies with 49.2% C and 50.8% T allelic frequencies while the CAT rs769217 polymorphism produced 79.6% C/C and 20.4% C/T genotype frequency with 89.8% C and 10.2% T allele frequency. Genotypes of all the 13 polymorphisms fitted the Hardy-Weinberg equilibrium.