Polymorphisms and linkage disequilibrium of the OATP8 (OATP1B3) gene in Japanese subjects.
OATP8, a member of the organic anion-transporting polypeptide family, is expressed on the sinusoidal membrane of hepatocytes, and transports endogenous organic anions, such as 17beta-glucuronosyl estradiol, and xenobiotic substances, such as digoxin. The objective of this study is to search for polymorphisms of the OATP8 gene and to assess the allele frequency of the polymorphisms in the Japanese population. Analysis of the OATP8 gene in 79 subjects revealed complete linkage of two deletion polymorphisms in the 5' regulatory region, deletion from position -28 to -11 and deletion from position -7 to -4, with an allele frequency of 0.196 for the deletion allele. The polymorphisms T334G (Ser112Ala) and G699A (Met233Ile) were also shown to be in complete linkage disequilibrium, with an allele frequency of 0.728 for the variant (112Ala/233Ile) allele. Interestingly, linkage disequilibrium was identified between the ins/del polymorphism and SNPs at 112 and 233. The predicted major haplotype was the insert-variant type with a haplotype frequency of 0.60.
Tsujimoto
Masayuki
M
Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Futuoka, Japan.
Hirata
Sumio
S
Dan
Yukihiko
Y
Ohtani
Hisakazu
H
Sawada
Yasufumi
Y
D000483:Alleles; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012313:RNA; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
D029362:Organic Anion Transporters, Sodium-Independent; C034477:RNA primers; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D012313:RNA