The potentially deleterious functional variant flavin-containing monooxygenase 2*1 is at high frequency throughout sub-Saharan Africa

Pharmacogenetics and Genomics

Volumn 18, Issue 10, 2008, Pages 877-886

  Veeramah, Krishna R ^a,b,c   Thomas, Mark G ^b   Weale, Michael E ^e   Zeitlyn, David ^f   Tarekegn, Ayele ^g   Bekele, Endashaw ^g   Mendell, Nancy R ^h   Shephard, Elizabeth A ^c,d   Bradman, Neil ^a   Phillips, Ian R ^a  

^a Centre for Genetic Anthropology

^b Research Department of Genetics Evolution and Environment

^c UNIVERSITY COLLEGE LONDON   (United Kingdom)

^d QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^e KING'S COLLEGE LONDON   (United Kingdom)

^f UNIVERSITY OF KENT   (United Kingdom)

^g ADDIS ABABA UNIVERSITY   (Ethiopia)

^h Stony Brook University   (United States)

Author keywords

Drug metabolism; Flavin containing monooxygenase; Flavin containing monooxygenase 2; Long range haplotype test; Pharmacogenetics; Sub Saharan Africa

Indexed keywords

DIMETHYLANILINE MONOOXYGENASE; FLAVIN CONTAINING MONOOXYGENASE 2; THIOUREA DERIVATIVE; UNCLASSIFIED DRUG;

ADULT; AFRICA; ARTICLE; DNA DETERMINATION; DRUG METABOLISM; EVOLUTION; GENE FREQUENCY; GENETIC VARIABILITY; GENOTYPE; GEOGRAPHIC ORIGIN; HAPLOTYPE; HUMAN; HUMAN EXPERIMENT; INCIDENCE; LUNG TOXICITY; MALE; NATURAL SELECTION; NORMAL HUMAN; PHARMACOGENETICS; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; STATISTICAL ANALYSIS;

ADOLESCENT; AFRICA SOUTH OF THE SAHARA; ALLELES; CHROMOSOME MAPPING; GENE FREQUENCY; GENOTYPE; HAPLOTYPES; HUMANS; LIKELIHOOD FUNCTIONS; LUNG; MALE; MUTATION; OXYGENASES; RISK; VARIATION (GENETICS);

MAMMALIA; PRIMATES;

EID: 53549126881     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e3283097311     Document Type: Article

References (42)

1. Cashman JR. Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab 2000; 1:181-191.
2. Phillips IR, Francois AA, Shephard EA. The flavin-containing monooxygenases (FMOs): genetic variation and its consequences for the metabolism of therapeutic drugs. Curr Pharmacogenomics 2007; 5:292-313.
3. Phillips IR, Shephard EA. Flavin-containing monooxygenases (FMOs): mutations, disease and drug response. Trends Pharmacol Sci 2008; 29:294-301.
4. Krueger SK, Williams DE. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism. Pharmacol Ther 2005; 106:357-387.
5. Lawton MP, Cashman JR, Cresteil T, Dolphin CT, Elfarra AA, Hines RN, et al. A nomenclature for the mammalian flavin-containing monooxygenase gene family based on amino acid sequence identities. Arch Biochem Biophys 1994; 308:254-257.
6. Phillips IR, Dolphin CT, Clair P, Hadley MR, Hutt AJ, McCombie RR, et al. The molecular biology of the flavin-containing monooxygenases of man. Chem Biol Interact 1995; 96:17-32.
7. Hernandez D, Janmohamed A, Chandan P, Phillips IR, Shephard EA. Organization and evolution of the flavin-containing monooxygenase genes of human and mouse: identification of novel gene and pseudogene clusters. Pharmacogenetics 2004; 14:117-130.
8. Hines RN, Hopp KA, Franco J, Saeian K, Begun FP. Alternative processing of the human FMO6 gene renders transcripts incapable of encoding a functional flavin-containing monooxygenase. Mol Pharmacol 2002; 62: 320-325.
9. Yueh MF, Krueger SK, Williams DE. Pulmonary flavin-containing monooxygenase (FMO) in rhesus macaque: expression of FMO2 protein, mRNA and analysis of the cDNA. Biochim Biophys Acta 1997; 1350: 267-271.
10. Dolphin CT, Beckett DJ, Janmohamed A, Cullingford TE, Smith RL, Shephard EA, Phillips IR. The flavin-containing monooxygenase 2 gene (FMO2) of humans, but not of other primates, encodes a truncated, nonfunctional protein. J Biol Chem 1998; 273:30599-30607.
11. Krueger SK, Yueh MF, Martin SR, Pereira CB, Williams DE. Characterization of expressed full-length and truncated FMO2 from rhesus monkey. Drug Metab Dispos 2001; 29:693-700.
12. Janmohamed A, Hernandez D, Phillips IR, Shephard EA. Cell-specific, tissue-specific, sex-specific and developmental stage-specific expression of mouse flavin-containing monooxygenases (Fmos). Biochem Pharmacol 2004; 68:73-83.
13. Whetstine JR, Yueh MF, McCarver DG, Williams DE, Park CS, Kang JH, et al. Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans. Toxicol Appl Pharmacol 2000; 168:216-224.
14. Krueger SK, Martin SR, Yueh MF, Pereira CB, Williams DE. Identification of active flavin-containing monooxygenase isoform 2 in human lung and characterization of expressed protein. Drug Metab Dispos 2002; 30:34-41.
15. Fumes B, Feng J, Sommer SS, Schlenk D. Identification of novel variants of the flavin-containing monooxygenase gene family in African-Americans. Drug Metab Dispos 2003; 31:187-193.
16. Krueger SK, Siddens LK, Martin SR, Yu Z, Pereira CB, Cabacungan ET, et al. Differences in FMO2*1 allelic frequency between Hispanics of Puerto Rican and Mexican descent. Drug Metab Dispos 2004; 32:1337-1340.
17. Henderson MC, Krueger SK, Siddens LK, Stevens JF, Williams DE. S-oxygenation of the thioether organophosphate insecticides phorate and disulfoton by human lung flavin-containing monooxygenase 2. Biochem Pharmacol 2004; 68:959-967.
18. Neal RA, Halpert J. Toxicology of thiono-sulfur compounds. Annu Rev Pharmacol Toxicol 1982; 22:321-339.
19. Henderson MC, Krueger SK, Stevens JF, Williams DE. Human flavincontaining monooxygenase form 2 S-oxygenation: sulfenic acid formation from thioureas and oxidation of glutathione. Chem Res Toxicol 2004; 17:633-640.
20. Krieter PA, Ziegler DM, Hill KE, Burk RF. Increased biliary GSSG efflux from rat livers perfused with thiocarbamide substrates for the flavin-containing monooxygenase. Mol Pharmacol 1984; 26:122-127.
21. Onderwater RC, Commandeur JN, Menge WM, Vermeulen NP. Activation of microsomal glutathione S-transferase and inhibition of cytochrome P450 1A1 activity as a model system for detecting protein alkylation by thioureacontaining compounds in rat liver microsomes. Chem Res Toxicol 1999; 12:396-402.
22. The Concise International Chemical Assessment Document 49 (CICADA 49). UN Environment Programme. Geneva, Switzerland: The International Labour Organization and the World Health Organization; 2003.
23. Vannelli TA, Dykman A, Ortiz de Montellano PR. The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase. J Biol Chem 2002; 277:12824-12829.
24. Fraaije MW, Kamerbeek NM, Heidekamp AJ, Fortin R, Janssen DB. The prodrug activator EtaA from Mycobacterium tuberculosis is a Baeyer-Villiger monooxygenase. J Biol Chem 2004; 279:3354-3360.
25. Qian L, Ortiz de Montellano PR. Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3. Chem Res Toxicol 2006; 19:443-449.
26. Reed TE. Caucasian genes in American Negroes. Science 1969; 165: 762-768.
27. Destro-Bisol G, Maviglia R, Caglia A, Boschi I, Spedini G, PascaJ V, et al. Estimating European admixture in African-Americans by using microsatellites and a microsatellite haplotype (CD4/Alu). Hum Genet 1999; 104:149-157.
28. Parra EJ, Marcini A, Akey J, Martinson J, Batzer MA, Cooper R, et al. Estimating African-American admixture proportions by use of populationspecific alleles. Am J Hum Genet 1998; 63:1839-1851.
29. Sabeti PC, Reich DE, Higgins JM, Levine HZ, Richter DJ, Schaffner SF, et al. Detecting recent positive selection in the human genome from haplotype structure. Nature 2002; 419:832-837.
30. Guo SW, Thompson EA. Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics 1992; 48:361-372.
31. Schneider S, Roessli D, Excoffier L Arlequin: a software for population genetics data analysis. User manual ver 2.000. Genetics and Biometry Lab. Department of Anthropology, University of Geneva; 2000.
32. Reynolds J, Weir BS, Cockerham CC. Estimation of the coancestry coefficient: basis for a short-term genetic distance. Genetics 1983; 105:767-779.
33. Voighl BF, Kudaravalli S, Wen X, Pntchard JK. A map of recent positive selection in the human genome. PLoS Biol 2006; 4:e72.
34. Griffiths RC, Marjoram P. Ancestral inference from samples of DNA sequences with recombination. J Comput Biol 1996; 3:479-502.
35. Cruciani F, Santolamazza P, Shen P, Macaulay V, Moral P, Otckers A, et al. A back migration from Asia to sub-Saharan Africa is supported by highresolution analysis of human Y-chromosome haplotypes. Am J Hum Genet 2002; 70:1197-1214.
36. Salas A, Richards M, De la FT, Lareu MV, Sobrino B, Sanchez-Diz P, et al. The making of the African mtDNA landscape. Am J Hum Genet 2002; 71:1082-1111.
37. Fisher HJ. Slavery in the history of muslim black Africa. Edition 1st. London: C. Hurst & Co. Ltd; 2001.
38. Richards M, Rengo C, Cruciani F, Gratrix F, Wilson JF, Scozzari R, et al. Extensive female-mediated gene flow from sub-Saharan Africa into near eastern Arab populations. Am J Hum Genet 2003; 72:1058-1064.
39. Cashman JR Some distinctions between flavin-containing and cytochrome P450 monooxygenases. Biochem Biophys Res Common 2005; 338:599-604.
40. Xue Y, Daly A, Yngvadottir B, Liu M, Coop G, Kim Y, et al. Spread of an inactive form of caspase-12 in humans is due to recent positive selection. Am J Hum Genet 2006; 78:659-670.
41. Mellars P. Why did modem human populations disperse from Africa ca. 60,000 years ago? A new model. Proc Natl Acad Sci USA 2006; 103:9381-9386.
42. Reed FA, Tishkoff SA. African human diversity, origins and migrations. Curr Opin Genet Dev 2006; 16:597-605.