Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations.
The extensive nucleotide diversity in drug-related genes predisposes individuals to different drug responses and is a major problem in current clinical practice and drug development. Striking allelic frequency differences exist in these genes between populations. In this study, we genotyped 240 sites known to be polymorphic in the Japanese population in each of 270 unrelated healthy individuals comprising 90 each of Malaysian Malays, Indians, and Chinese. These sites are distributed in 109 genes that are drug related, such as genes encoding drug-metabolizing enzymes and drug transporters. Allele frequency and linkage disequilibrium distributions of these sites were determined and compared. They were also compared with similar data of 752 Japanese. Extensive similarities in allele frequency and linkage disequilibrium distributions were observed among Japanese, Malaysian Chinese, and Malays. However, significant differences were observed between Japanese and Malaysian Chinese with Malaysian Indians. These four populations were grouped into two genetic clusters of different ancestries. However, a higher correlation was found between Malaysian Malays and Indians, indicating the existence of extensive admixture between them. The results also imply the possible and rational use of existing single nucleotide polymorphism databases as references to assist future pharmacogenetic studies involving populations of similar ancestry.
Cha
Pei-Chieng
PC
Institute of Biological Sciences (Genetics and Molecular Biology), Faculty of Science, University of Malaya, 50603, Lembah Pantai, Kuala Lumpur, Malaysia. genescha@yahoo.com.
Yamada
Ryo
R
Laboratory for Rheumatic Diseases, SNP Research Center (SRC), Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Sekine
Akihiro
A
Laboratory for Genotyping, SRC, RIKEN, Yokohama, Japan.
Nakamura
Yusuke
Y
Research Group for Personalized Medicine, SRC, RIKEN, Yokohama, Japan.|Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Koh
Chong-Lek
CL
Institute of Biological Sciences (Genetics and Molecular Biology), Faculty of Science, University of Malaya, 50603, Lembah Pantai, Kuala Lumpur, Malaysia.
D000483:Alleles; D005787:Gene Frequency; D005819:Genetic Markers; D006801:Humans; D015810:Linkage Disequilibrium; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D005819:Genetic Markers