The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa.
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 non-functional variant, FMO2*2A, which contains a...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Wolters Kluwer
2008
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| _version_ | 1797074352498278400 |
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| author | Veeramah, K Thomas, MG Weale, M Zeitlyn, D Tarekegn, A Bekele, E Mendell, N Shephard, E Bradman, N Phillips, I |
| author_facet | Veeramah, K Thomas, MG Weale, M Zeitlyn, D Tarekegn, A Bekele, E Mendell, N Shephard, E Bradman, N Phillips, I |
| author_sort | Veeramah, K |
| collection | OXFORD |
| description | 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 non-functional 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. |
| first_indexed | 2024-03-06T23:34:53Z |
| format | Journal article |
| id | oxford-uuid:6d52cc20-d594-4827-9c0b-d9dfda514d10 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:34:53Z |
| publishDate | 2008 |
| publisher | Wolters Kluwer |
| record_format | dspace |
| spelling | oxford-uuid:6d52cc20-d594-4827-9c0b-d9dfda514d102022-03-26T19:17:00ZThe potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6d52cc20-d594-4827-9c0b-d9dfda514d10EnglishSymplectic Elements at OxfordWolters Kluwer2008Veeramah, KThomas, MGWeale, MZeitlyn, DTarekegn, ABekele, EMendell, NShephard, EBradman, NPhillips, IBACKGROUND: 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 non-functional 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. |
| spellingShingle | Veeramah, K Thomas, MG Weale, M Zeitlyn, D Tarekegn, A Bekele, E Mendell, N Shephard, E Bradman, N Phillips, I The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. |
| title | The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. |
| title_full | The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. |
| title_fullStr | The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. |
| title_full_unstemmed | The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. |
| title_short | The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa. |
| title_sort | potentially deleterious functional variant flavin containing monooxygenase 2 1 is at high frequency throughout sub saharan africa |
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