Open AccessNovel CYP2E1 haplotype identified in a South African cohort
Author(s) -
Laura Jane Heathfield,
Shareefa Dalvie,
Kusha Kalideen,
Collet Dandara
Publication year - 2014
Publication title -
south african journal of science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.317
H-Index - 61
eISSN - 1996-7489
pISSN - 0038-2353
DOI - 10.1590/sajs.2014/20130324
Subject(s) - haplotype , aldh2 , cyp2e1 , single nucleotide polymorphism , adh1b , genetics , alcohol dehydrogenase , biology , population , aldehyde dehydrogenase , snp , genotype , allele frequency , allele , medicine , alcohol , gene , enzyme , biochemistry , environmental health , dehydrogenase , branched chain alpha keto acid dehydrogenase complex , in vitro , microsome
Alcohol abuse accounts for approximately 2.5 million deaths annually and is the third highest risk factor for disease and disability. Alcohol is metabolised by polymorphic enzymes and the status of an individual with respect to alcohol metabolising enzymes may have forensic relevance in post-mortems. Baseline frequencies of gene variants involved in alcohol metabolism need to be established to aid the identification of suitable population-specific polymorphisms to genotype during molecular autopsies. The principal alcohol metabolising enzymes include alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1). Six single nucleotide polymorphisms (SNPs) – rs1229984G>A and rs2066702C>T in ADH1B, rs671G>A in ALDH2, and rs3813867G>C, rs2031920C>T and rs6413432T>A in CYP2E1 – were genotyped in 150 individuals from four South African populations: Xhosa, Zulu, South African white and South African coloured. Allele frequencies for each SNP in the four population groups were 0–10% for rs1229984A, 2–12% for rs2066702T, 0–2% for rs671A, 1–4% for rs3813867C, 0–1% for rs2031920T and 3–15% for rs6413432A. Haplotype analysis revealed a novel combination of three SNPs in CYP2E1 whose effects on alcohol metabolism need further investigation. Establishment of baseline frequencies adds to our knowledge of genetic variation in alcohol metabolising enzymes and additional research is required to determine the functional significance of this novel CYP2E1 haplotype