Literature DB >> 15355885

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

Sharon K Krueger1, Lisbeth K Siddens, Sarah R Martin, Zhen Yu, Clifford B Pereira, Erwin T Cabacungan, Ronald N Hines, Kristin G Ardlie, Judy L Raucy, David E Williams.   

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%.

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Year:  2004        PMID: 15355885     DOI: 10.1124/dmd.104.001099

Source DB:  PubMed          Journal:  Drug Metab Dispos        ISSN: 0090-9556            Impact factor:   3.922


  15 in total

1.  Mammalian flavin-containing monooxygenase (FMO) as a source of hydrogen peroxide.

Authors:  Lisbeth K Siddens; Sharon K Krueger; Marilyn C Henderson; David E Williams
Journal:  Biochem Pharmacol       Date:  2014-02-19       Impact factor: 5.858

Review 2.  Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism.

Authors:  Sharon K Krueger; David E Williams
Journal:  Pharmacol Ther       Date:  2005-06       Impact factor: 12.310

3.  Haplotype and functional analysis of four flavin-containing monooxygenase isoform 2 (FMO2) polymorphisms in Hispanics.

Authors:  Sharon K Krueger; Lisbeth K Siddens; Marilyn C Henderson; Eric A Andreasen; Robert L Tanguay; Clifford B Pereira; Erwin T Cabacungan; Ronald N Hines; Kristin G Ardlie; David E Williams
Journal:  Pharmacogenet Genomics       Date:  2005-04       Impact factor: 2.089

4.  Characterization of sulfoxygenation and structural implications of human flavin-containing monooxygenase isoform 2 (FMO2.1) variants S195L and N413K.

Authors:  Sharon K Krueger; Marilyn C Henderson; Lisbeth K Siddens; Jonathan E VanDyke; Abby D Benninghoff; P Andrew Karplus; Bjarte Furnes; Daniel Schlenk; David E Williams
Journal:  Drug Metab Dispos       Date:  2009-05-06       Impact factor: 3.922

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

Authors:  Krishna R Veeramah; Mark G Thomas; Michael E Weale; David Zeitlyn; Ayele Tarekegn; Endashaw Bekele; Nancy R Mendell; Elizabeth A Shephard; Neil Bradman; Ian R Phillips
Journal:  Pharmacogenet Genomics       Date:  2008-10       Impact factor: 2.089

6.  A genome-wide survey of the prevalence and evolutionary forces acting on human nonsense SNPs.

Authors:  Bryndis Yngvadottir; Yali Xue; Steve Searle; Sarah Hunt; Marcos Delgado; Jonathan Morrison; Pamela Whittaker; Panos Deloukas; Chris Tyler-Smith
Journal:  Am J Hum Genet       Date:  2009-02-05       Impact factor: 11.025

7.  Flavin-containing monooxygenase S-oxygenation of a series of thioureas and thiones.

Authors:  Marilyn C Henderson; Lisbeth K Siddens; Sharon K Krueger; J Fred Stevens; Karen Kedzie; Wenkui K Fang; Todd Heidelbaugh; Phong Nguyen; Ken Chow; Michael Garst; Daniel Gil; David E Williams
Journal:  Toxicol Appl Pharmacol       Date:  2014-04-12       Impact factor: 4.219

8.  Characterization of mouse flavin-containing monooxygenase transcript levels in lung and liver, and activity of expressed isoforms.

Authors:  Lisbeth K Siddens; Marilyn C Henderson; Jonathan E Vandyke; David E Williams; Sharon K Krueger
Journal:  Biochem Pharmacol       Date:  2007-09-08       Impact factor: 5.858

9.  Metabolism of the anti-tuberculosis drug ethionamide by mouse and human FMO1, FMO2 and FMO3 and mouse and human lung microsomes.

Authors:  Marilyn C Henderson; Lisbeth K Siddens; Jeffrey T Morré; Sharon K Krueger; David E Williams
Journal:  Toxicol Appl Pharmacol       Date:  2008-10-01       Impact factor: 4.219

10.  Metabolism and pharmacokinetics of the anti-tuberculosis drug ethionamide in a flavin-containing monooxygenase null mouse.

Authors:  Amy L Palmer; Virginia L Leykam; Andrew Larkin; Sharon K Krueger; Ian R Phillips; Elizabeth A Shephard; David E Williams
Journal:  Pharmaceuticals (Basel)       Date:  2012
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