Haplotype Frequency Distribution and Linkage Disequilibrium Analysis of Single Nucleotide Polymorphisms at the Human FMO3 Gene Locus |
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Authors: | Da-Cheng Hao Jie Sun Bjarte Furnes Daniel Schlenk Zhen-Fang Hou Ya-Ping Zhang Sheng-Li Yang Ling Yang |
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Institution: | (1) Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China;(2) Department of Emergency Medicine, Dalian Medical University, Dalian, China;(3) Environmental Toxicology Program, University of California, Riverside, CA, USA;(4) The Graduate School, Chinese Academy of Sciences, Beijing, China;(5) Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China |
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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. |
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Keywords: | FMO3 polymorphism haplotype frequency linkage evolution |
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