Frequencies of single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in a Finnish population

Objective: Organic anion transporting polypeptide 1B1 (OATP1B1) is a drug uptake transporter located at the sinusoidal membrane of hepatocytes. Our aim was to establish high-throughput genotyping assays for the major known single nucleotide polymorphisms (SNP) in the SLCO1B1 gene encoding OATP1B1 and to investigate the frequencies of SNPs and haplotypes of SLCO1B1 in a large Caucasian population. Methods: Distribution of SLCO1B1 alleles was determined in 468 healthy Finnish Caucasian subjects at 11 variant sites spanning the entire gene by using allelic discrimination with TaqMan 5' nuclease assays. Results: The allelic frequencies of SLCO1B1 SNPs were 9.7% for g.-11187G > A, 0.4% for g.-11110T > G, 8.0% for g.-10499A > C, 46.2% for c.388A > G, 13.1% for c.411G > A, 13.1% for c.463C > A, 20.2% for c.521T > C, 53.2% for c.571T > C, 46.4% for c.597C > T, 4.0% for c.1929A > C and 48.8% for c.*439T > G. Altogether, 26 haplotypes were statistically inferred. The most common haplotype, with a frequency of 35.6%, contained variant allele C at position c.571, but had the reference nucleotide at all other positions investigated. The functionally significant c.521T > C SNP existed in four major haplotypes, which could be differentiated by the g.-11187G > A, g.-10499A > C and c.388A > G SNPs. The frequencies of these haplotypes were 7.9% for g.-11187G/g.-10499C/c.388G/c.521C (*16), 6.9% for AAGC (*17), 2.7% for GAAC (*5) and 2.4% for GAGC (*15). Conclusion: Sequence variations of SLCO1B1 occur at high frequencies in the Caucasian population. Further studies are needed to characterise the effects of SLCO1B1 haplotypes, especially *16, *17, *15 and *5, on drug pharmacokinetics and response, and to determine the frequencies of SLCO1B1 SNPs and haplotypes in different populations.