Received for publication June 22, 2004.
Revised August 26, 2004.
Accepted for publication September 7, 2004.

Differences in FMO2*1 allelic frequency between Hispanics of Puerto Rican and Mexican descent

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 inter-ethnic differences in allelic frequency. FMO2 is the major or sole FMO isoform expressed in the lung of most mammals, including non-human 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 individuals of Mexican descent (2%). The overall occurrence of FMO2*1 among Hispanics of all origins is estimated to be between 2 and 7%.

Key words: ethnic differences, extrahepatic drug metabolism, flavin-containing monooxygenase, genetic polymorphism, human genetics, inhalation toxicology, pharmacogenetics, polymorphisms, pulmonary metabolism

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