Veeramah, Krishna R. and Thomas, Mark G. and Weale, Michael E. and Zeitlyn, David and Tarekegn, Ayele and Bekele, Endashaw and Mendell, Nancy R. and Shephard, Elizabeth A. and Bradman, Neil and Phillips, Ian R. (2008) The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. Pharmacogenetics and Genomics, 18 (10). pp. 877-886. ISSN 1744-6872.
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Background The drug-metabolizing enzyme flavin-containing monooxygenase 2 (FMO2) is the predominant FMO isoform present in the lung of most mammals, including non-human primates. All Europeans and Asians tested have been shown to be homozygous for a nonfunctional variant, FMO2*2A, which contains a premature stop codon due to a single-nucleotide change in exon 9 (g.23238C > T). The ancestral allele, FMO2*1, encodes a functionally active protein and has been found in African-Americans (26%) and Hispanics (2% to 7%). Possessing this variant increases the risk of pulmonary toxicity when exposed to thioureas, a widely used class of industrial compounds. FMO2 may also be involved in the metabolism of drugs that are used to treat diseases that are prevalent in Africa. Results and Conclusion We conducted a survey of g.23238C > T variation across Africa that revealed that the distribution of this SNP is relatively homogeneous across sub-Saharan Africa, with approximately one third of individuals possessing at least one FMO2*1 allele, though in some populations the incidence of these individuals approached 50%. Thus many sub-Saharan Africans may be at substantially increased health risk when encountering thiourea-containing substrates of FMO2. Analysis of HapMap data with the Long-Range Haplotype test found no evidence for positive selection of either 23238C > T allele and maximum-likelihood coalescent analysis indicated that this mutation occurred some 500,000 years before present. This study demonstrates the value of performing genetic surveys in Africa, a continent in which human genetic diversity is thought to be greatest, but where studies of the distribution of this diversity are few.
|Uncontrolled keywords:||drug metabolism; flavin-containing monooxygenase; flavin-containing monooxygenase 2; long-range haplotype test; pharmacogenetics; sub-Saharan Africa|
|Subjects:||G Geography. Anthropology. Recreation > GF Human ecology. Anthropogeography
G Geography. Anthropology. Recreation > GN Anthropology
|Divisions:||Faculties > Social Sciences > School of Anthropology and Conservation > Social and Cultural Anthropology
Faculties > Social Sciences > School of Anthropology and Conservation > Biological Anthropology
|Depositing User:||D. Zeitlyn|
|Date Deposited:||24 Mar 2009 16:04|
|Last Modified:||14 Jan 2010 14:46|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/11755 (The current URI for this page, for reference purposes)|
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