Ethnic differences of FMO3 gene mutant alleles

Recently, genetic linkage between two common FMO3 mutations (Glu¹⁵⁸→Lys and Glu³⁰⁸→Gly) was found in Koreans. These FMO3 mutations were closely associated with diminished FMO activity catalyzing (ranitidine N-oxidation). To compare the frequencies of these FMO3 mutant alleles among Koreans, Caucasians and African-Americans, we determined the presence of Lys¹⁵⁸ and Gly³⁰⁸ mutant alleles using HinfI and DraII. Following results were obtained: Population N Lys¹⁵⁸ Ply³⁰⁸ Korean 219 0.19 0.18 Caucasian 55 0.40 0.20 African-American 194 0.39 0.06 The Lys¹⁵⁸ allele was found more frequently in Caucasians and African-Americans (p<0.001). However, the Gly³⁰⁸ allele was found more frequently in Koreans and Caucasians (p<0.001). While these two common mutations were found to be linked in Koreans, they did not appear to be linked in Caucasians and African-Americans. As FMO3/Gly³⁰⁸ mutation was correlated with decreased FMO activity in Koreans, high frequency of its appearance in Caucasians suggests their FMO activity would be lower than that of African-Americans. We conclude that there is a remarkable ethnic difference in FMO3 mutant allele frequencies and their genetic linkage.