title: Haplotype frequency distribution and linkage disequilibrium analysis of single nucleotide polymorphisms at the human FMO3 gene locus.
abstract: We analyzed flavin-containing monooxygenase 3 (FMO3) polymorphisms, haplotype structure, and linkage disequilibrium (LD) in 256 Han Chinese and 50 African-American individuals to compare their haplotype frequencies and LD with other world populations. For the Han Chinese, genotyping of three haplotype tag single nucleotide polymorphisms (E158K, V257M, and E308G) was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism. For the African-Americans, genotyping of all coding exons was performed by modified PCR-single strand conformational polymorphism. Haplotype frequencies, LD, and evolutionary rates were inferred and estimated computationally. There were significant differences in haplotype frequency distribution and LD pattern among Han Chinese, African-Americans, and other world populations. Four major haplotypes of Han Chinese were EVE, KVE, EME, and EVG. Two major haplotypes of African-Americans were EVE and KVE. We found that sites 158 and 257 are in significant LD in both populations. This is the first report comparing FMO haplotypes and LD of Han Chinese with African-Americans. The data presented here justify further pharmacogenetic studies for potentially optimizing recommended drug dosages and evaluating relationships with disease processes.
authors.affiliation: Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Da-Cheng
authors.initials: DC
authors.lastname: Hao
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Bjarte
authors.initials: B
authors.lastname: Furnes
authors.forename: Daniel
authors.initials: D
authors.lastname: Schlenk
authors.forename: Zhen-Fang
authors.initials: ZF
authors.lastname: Hou
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
mesh_terms: D000328:Adult; D001741:Black or African American; D000818:Animals; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002681:China; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010105:Oxygenases / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017386:Sequence Homology, Amino Acid
chemical_list: D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)