title: Frequencies of single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in a Finnish population.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, PO Box 340, Helsinki, 00029 HUS, Finland.
authors.forename: Marja K
authors.initials: MK
authors.lastname: Pasanen
authors.forename: Janne T
authors.initials: JT
authors.lastname: Backman
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Niemi
mesh_terms: D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005387:Finland; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D017931:DNA Primers; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human