Flavin-containing monooxygenase 3 polymorphisms in 13 ethnic populations from Europe, East Asia and sub-Saharan Africa: frequency and linkage analysis.
OBJECTIVE
To investigate intra- and inter-ethnic differences in three widespread (E158K, V257M and E308G) and two African-specific (D132H and L360P) flavin-containing monooxygenase 3 (FMO3) polymorphisms.


METHODS
Allele frequencies were determined by TaqMan allelic discrimination assay in 2152 healthy volunteers from Europe (Swedes, Italians and Turks), East Asia (Japanese) and sub-Saharan Africa (nine ethnic groups covering eastern, southern and western regions), followed by haplotype and linkage analysis.


RESULTS
Significant subpopulation differences (p < 0.001) in allele frequencies were found for E158K, V257M and E308G in Europeans and regional differences (p < 0.01) for D132H among Africans. No carrier of P360 was identified. Cis-linkage between G308 and K158 was confirmed with the compound variant (K158/G308) being found in a high proportion (12.0-38.3%) of non-African subjects, but rarely (1.3%) among Africans.


CONCLUSIONS
Distribution of functionally relevant FMO3 polymorphisms varies not only between ethnicities but also within. The K158/G308 variant may have potential clinical importance primarily in non-African populations due to its low prevalence in Africa.
Mao
Mao
M
Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. mao.mao@medsci.uu.se
Matimba
Alice
A
Scordo
Maria G
MG
Gunes
Arzu
A
Zengil
Hakan
H
Yasui-Furukori
Norio
N
Masimirembwa
Collen
C
Dahl
Marja-Liisa
ML
D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D005006:Ethnicity; D005060:Europe / Q000453:epidemiology; D005202:Asia, Eastern / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D010105:Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)