Novel Haplotypes of genetic polymorphisms in alcohol metabolizing enzymes in Kampala, Uganda

Background Alcohol is metabolized to acetaldehyde by alcohol dehydrogenases (ADH) and subsequently to acetate by aldehyde dehydrogenases (ALDH). Single nucleotide polymorphisms (SNPs) in ADH1B, ADH1C and ALDH2 genes lead to haplotypes encoding isozymes which influence development of alcoholism. The distribution of these haplotypes in Uganda has not been documented. The aim of this study was to determine genotype, allele, and haplotype frequencies of SNPs in ADH1B, ADH1C , and ALDH2 genes in Uganda. Results Five SNPs: ADH1B (rs1229984 and rs2066702), ADH1C (rs1693482 and rs698) and ALDH2 (rs671) were analyzed by PCR-restriction fragment length polymorphism assays in 250 samples. The frequencies of the fast-metabolizing alleles ADH1C*1 , ADH1B*3 , and ADH1B*2 were 49.6%, 18.2% and 0.2% respectively. The nonprotective haplotype ADH1B *1 had a high frequency of 81.6% and ADH1C*2 was 10.6%. A novel allele ADH1C*new comprising G (Codon 349 Val) at ADH1C rs698 and G (Codon 271 Arg) at ADH1C rs1693482 was identified with a frequency of 39.8%. Of the seven ADH haplotype combinations identified, ADH1B *1- ADH1C *1 was the most prevalent (48.4%). Notably ADH1B*1–ADH1C* new , had the second highest frequency (25.2%). Conclusion Our study provides the first data on novel ADH1B-ADH1C haplotypes in alcohol metabolizing genes in the Ugandan population.