Abstract
A polymorphism for the phase I drug-metabolizing enzyme, flavin-containing monooxygenase isoform 2 (FMO2), encoding either truncated inactive protein, FMO2X472 (FMO2.2A), or full-length active enzyme, FMO2Q472 (FMO2.1), is known and exhibits significant interethnic differences in allelic frequency. FMO2 is the major or sole FMO isoform expressed in the lung of most mammals, including nonhuman primates. To date, FMO2.1 has been found only in African-American and Hispanic populations, rendering individuals with this allele subject to drug metabolism that is potentially different from that of the general population. Approximately 26% of African-Americans (n = 180) possess the FMO2*1 allele. In preliminary studies, we initially estimated that 5% of Hispanics (n = 40) have the FMO2*1 allele, but access to large cohorts of individuals of defined national origin has allowed us to determine the occurrence among Mexican-American and Puerto Rican-American groups. We used allele-specific genotyping to detect FMO2*1 from 632 Hispanic individuals, including 280 individuals of Mexican origin and 327 individuals of Puerto Rican origin. Statistical analysis indicated that results from Mexican (five sample sources) and Puerto Rican (three sample sources) samples were consistent with the hypothesis of homogeneity within each group from different sources. Data were subsequently pooled across sources to test for evidence of a difference in occurrence of FMO2*1 between ethnic groups. There was strong evidence (p = 0.0066) that FMO2*1 is more common among Puerto Ricans (7%) than among individuals of Mexican descent (2%). The overall occurrence of FMO2*1 among Hispanics of all origins is estimated to be between 2 and 7%.
Footnotes
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This study was supported by United States Public Health Service Grants HL38650 and ES00210. Part of this study was presented at the 41st Annual Meeting of the Society of Toxicology, Nashville, Tennessee, March 2002, an abstract of which appeared in The Toxicologist 66(1-S),189. Part of this study was also presented at the Second International workshop on Trimethylaminuria, Washington, D.C., USA, March 2002.
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doi:10.1124/dmd.104.001099.
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ABBREVIATIONS: FMO, flavin-containing monooxygenase; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism
- Received June 18, 2004.
- Accepted September 7, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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