Frequency of the SLCO1B1 388A > G and the 521T > C polymorphism in Tanzania genotyped by a new LightCycler (R)-based method

Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge C-168, Karolinska Institute, SE-141 86 Stockholm, Sweden.
European Journal of Clinical Pharmacology (Impact Factor: 2.97). 06/2011; 67(11):1139-45. DOI: 10.1007/s00228-011-1065-9
Source: PubMed


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.
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.
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%).
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.

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Available from: Eleni Aklillu
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    • "The interpretations of allelic, genotype and haplotype frequency distributions from this study are in agreement with similar population studies that have been carried out in Chinese (10), Tanzanian (25), Brazilian (26, 27), Caucasian, African, and East Asian (28, 29), Canadian (30), Finnish (31), German and Turkish (32), African American and Hispanic populations (20, 33). One large scale study on the global analysis of genetic variations in SLCO1B1 (5) compared several populations for their allele and genotype frequencies and found that there was no significant difference within the groups of a population; however, a large variability existed when populations were compared with each other or in such haplotypes where alleles occurred in a linkage disequilibrium with each other. "
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