Frequency distribution of human FMO3 gene in two genetically distinct populations: single nucleotide polymorphisms

Aims: To analyze the flavin-containing monooxygenase 3 (FMO3) polymorphisms, haplotype structure, and linkage disequilibrium (LD) in 256 Han Chinese and 50 African-American individuals, to compare the allele, genotype, and haplotype frequencies of these populations with those of other world populations. Methods: For Han Chinese, genotyping of three common single nucleotide polymorphisms, E158K, V257M, E308G, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). For African-Americans, genotyping of all coding exons was performed by modified PCR-single strand conformational polymorphism (SSCP). Results: There were significant differences in allele and genotype frequencies, haplotype frequency distribution, and LD pattern among Han Chinese, African-Americans, and other world populations. In Han Chinese, the minor allele frequencies (MAFs) were 0.229 (E158K, 95% CI: 0.193-0.265), 0.203 (V257M, 95% CI: 0.168-0.238), and 0.148 (E308G, 95% CI: 0.117-0.179), respectively. In African-Americans, MAFs were 0.48 (E158K, 95% CI: 0.382-0.578), 0.05 (V257M, 95% CI: 0.007-0.093), 0 (E308G), respectively. Four major haplotypes (MHs) of Han Chinese were EVE (relative frequency: 0.4460, 95% CI: 0.4090-0.4829), KVE (0.1921, 95% CI: 0.1652-0.2190), EME (0.1645, 95% CI: 0.1440-0.1850), and EVG (0.1327, 95% CI: 0.1105-0.1548). Two MHs of African-Americans were EVE (0.4895, 95% CI: 0.4696-0.5093) and KVE (0.4605, 95% CI: 0.4407-0.4804). We found that sites 158 and 257 are in significant LD in both populations, there are more relatively rare haplotypes in the Chinese female group than in the male group (P=0.0085), and there was rapid evolution during the divergence of primate FMO3. Conclusion: The data presented here justify further pharmacogenetic studies for potentially optimizing recommended drug dosages and evaluating relationships with disease processes