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

  • Pharmacogenetics
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Abstract

Purpose

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.

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Acknowledgements

This work was partly supported by a grant of the European and Developing Countries Clinical Trials Partnership (EDCTP CT.2005.32030.001). We thank Jutta Kocher for excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge C-168, Karolinska Institute, SE-141 86, Stockholm, Sweden

    Eleni Aklillu & Eliford Ngaimisi

  2. Department of Internal Medicine, Muhimbili National Hospital, Dar es Salaam, Tanzania

    Sabina Mugusi

  3. Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

    Eliford Ngaimisi

  4. Division of Clinical Chemistry, Department of Medicine, Albert-Ludwigs-University, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Michael Marcus Hoffmann

  5. Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Sonja König, Victoria Ziesenitz, Gerd Mikus, Walter Emil Haefeli & Johanna Weiss

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  1. Eleni Aklillu
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Correspondence to Johanna Weiss.

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Aklillu, E., Mugusi, S., Ngaimisi, E. et al. Frequency of the SLCO1B1 388A>G and the 521T>C polymorphism in Tanzania genotyped by a new LightCycler®-based method. Eur J Clin Pharmacol 67, 1139–1145 (2011). https://doi.org/10.1007/s00228-011-1065-9

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  • DOI: https://doi.org/10.1007/s00228-011-1065-9

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