title: Frequency of the SLCO1B1 388A>G and the 521T>C polymorphism in Tanzania genotyped by a new LightCycler®-based method.
abstract: OBJECTIVE
  The 388A>G and the 521T>C polymorphism of the SLCO1B1 gene affect the activity of the uptake transporter OATP1B1, thus influencing kinetics, safety, and efficacy of substrate drugs. To evaluate the impact of these polymorphisms in populations of different ethnic origins, it is important to know their frequencies and to develop fast and reliable methods for genotyping. We therefore established a new, high-throughput method and determined the genotype and allelic frequencies of these polymorphisms in Tanzanians, for which the frequencies were unknown thus far.
  
  
  METHODS
  New LightCycler® 480-based methods with hybridization probes were established and used to genotype 366 Tanzanian and 236 European individuals for 388A>G (rs2306283) and 521T>C (rs4149056) in the SLCO1B1 gene. The methods were validated by direct sequencing of the polymerase chain reaction (PCR) products of heterozygous individuals and checked for intrarun precision repeatability, interrun precision reproducibility, robustness, and deviations from the Hardy-Weinberg equilibrium.
  
  
  RESULTS
  The new methods allow unambiguous identification of the corresponding genotypes. There was a clear difference in allelic distribution between Tanzanians and Europeans, with the 388A>G (rs2306283) being much more prevalent in Tanzanians (87% vs 41%) and the 521T>C (rs4149056) being very rare in this African population (6% vs 17%).
  
  
  CONCLUSIONS
  We developed robust and high-throughput methods to genotype common SLCO1B1 allelic variants with the LightCycler® 480. In Tanzanians, we identified the highest frequency of the 388A>G and 521T>C polymorphisms ever reported from black populations. The clinical relevance of SLCO1B1 genetic variation in the African population remains to be investigated.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge C-168, Karolinska Institute, SE-141 86 Stockholm, Sweden.
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
authors.forename: Sabina
authors.initials: S
authors.lastname: Mugusi
authors.forename: Eliford
authors.initials: E
authors.lastname: Ngaimisi
authors.forename: Michael Marcus
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Sonja
authors.initials: S
authors.lastname: König
authors.forename: Victoria
authors.initials: V
authors.lastname: Ziesenitz
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
authors.forename: Walter Emil
authors.initials: WE
authors.lastname: Haefeli
authors.forename: Johanna
authors.initials: J
authors.lastname: Weiss
mesh_terms: D044383:Black People / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods*; D013636:Tanzania; D044465:White People / Q000235:genetics
chemical_list: D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D004247:DNA