SLCO1B1 Gene Variations Among Tanzanians, Ethiopians, and Europeans: Relevance for African and Worldwide Precision Medicine - PubMed

SLCO1B1 Gene Variations Among Tanzanians, Ethiopians, and Europeans: Relevance for African and Worldwide Precision Medicine

Eleni Aklillu et al. OMICS. 2016 Sep.

Abstract

The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound organic anion transporter protein involved in active cellular influx of many endogenous compounds and xenobiotics. SLCO1B1 genetic variation is associated, for example, with highly variable rifampicin exposure, thus influencing the cornerstone antituberculosis therapy, especially in sub-Saharan Africa where it is a key therapeutic modality. Yet, there is no SLCO1B1-guided pharmacogenetic dosing recommendation for rifampicin to reduce the risk of adverse events or therapy failure. Accordingly, comparative characterization of SLCO1B1, particularly within understudied African populations, is crucial and timely for global precision medicine, given the importance of antituberculosis therapy worldwide. Therefore, we report here the allele, genotype, and haplotype frequencies for common SLCO1B1 gene polymorphisms among Europeans (N = 57), Tanzanians (N = 361), and Ethiopians (N = 632). Our results show that the allele frequencies of rs4149032T, rs2306283G, rs11045819A, and rs4149056C differ significantly among Ethiopians (48.1%, 60.3%, 2.8%, 19.1%). Tanzanians (51.9%, 86.8%, 4.7%, 3.2%), and Europeans (19.8%, 34.2%, 7.9%, 22.8%) (p < 0.001). Notably, the most common haplotypes in Tanzanians (TGCT; g.38664T + c.388G + c.463C + c.521T = 61.1%) and Europeans (CGCT, all wild-type SLCO1B*1A = 59.8%) occurred at a much lower frequency in Ethiopians (TGCT = 38.8% and CGCT = 31.6%) (p < 0.0001). Additionally, the nonfunctional SLCO1B1 haplotypes CGCC (*15) and CACC (*5) are relatively common or detectable in Ethiopians (14.1%, 3.2%, respectively) and Europeans (18.1%, 2.8%) but rare in Tanzanians (1.9% and 0%, respectively) (p < 0.001). These new observations collectively underscore that precision medicine for rifampicin and other cornerstone therapeutics will require a comparative study of each and every population in the African continent as well as globally. SLCO1B1 and its extensive within- and between-population variations have to be carefully borne in mind for global precision medicine.

Similar articles

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

  Pasanen MK, Backman JT, Neuvonen PJ, Niemi M. Pasanen MK, et al. Eur J Clin Pharmacol. 2006 Jun;62(6):409-15. doi: 10.1007/s00228-006-0123-1. Epub 2006 Apr 21. Eur J Clin Pharmacol. 2006. PMID: 16758257

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

  Aklillu E, Mugusi S, Ngaimisi E, Hoffmann MM, König S, Ziesenitz V, Mikus G, Haefeli WE, Weiss J. Aklillu E, et al. Eur J Clin Pharmacol. 2011 Nov;67(11):1139-45. doi: 10.1007/s00228-011-1065-9. Epub 2011 Jun 1. Eur J Clin Pharmacol. 2011. PMID: 21630030

• Mapping SLCO1B1 Genetic Variation for Global Precision Medicine in Understudied Regions in Africa: A Focus on Zulu and Cape Admixed Populations.

  Hoosain N, Pearce B, Jacobs C, Benjeddou M. Hoosain N, et al. OMICS. 2016 Sep;20(9):546-54. doi: 10.1089/omi.2016.0115. OMICS. 2016. PMID: 27631194

• SLCO1B1 polymorphism and oral antidiabetic drugs.

  Kalliokoski A, Neuvonen PJ, Niemi M. Kalliokoski A, et al. Basic Clin Pharmacol Toxicol. 2010 Oct;107(4):775-81. doi: 10.1111/j.1742-7843.2010.00581.x. Basic Clin Pharmacol Toxicol. 2010. PMID: 20406215 Review.

• The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy.

  Romaine SP, Bailey KM, Hall AS, Balmforth AJ. Romaine SP, et al. Pharmacogenomics J. 2010 Feb;10(1):1-11. doi: 10.1038/tpj.2009.54. Epub 2009 Nov 3. Pharmacogenomics J. 2010. PMID: 19884908 Review.

Cited by

• Conference report: pharmacogenomics in special populations at WCP2018.

  Suarez-Kurtz G, Aklillu E, Saito Y, Somogyi AA. Suarez-Kurtz G, et al. Br J Clin Pharmacol. 2019 Mar;85(3):467-475. doi: 10.1111/bcp.13828. Epub 2019 Jan 24. Br J Clin Pharmacol. 2019. PMID: 30537134 Free PMC article.

• Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations.

  Bedada W, de Andrés F, Engidawork E, Hussein J, LLerena A, Aklillu E. Bedada W, et al. Sci Rep. 2018 Aug 24;8(1):12726. doi: 10.1038/s41598-018-31191-1. Sci Rep. 2018. PMID: 30143732 Free PMC article.

• Variability in plasma rifampicin concentrations and role of SLCO1B1, ABCB1, AADAC2 and CES2 genotypes in Ethiopian patients with tuberculosis.

  Sileshi T, Makonnen E, Telele NF, Barclay V, Zumla A, Aklillu E. Sileshi T, et al. Infect Dis (Lond). 2024 Apr;56(4):308-319. doi: 10.1080/23744235.2024.2309348. Epub 2024 Feb 5. Infect Dis (Lond). 2024. PMID: 38315168

• N-Acetyltransferase-2 (NAT2) phenotype is influenced by genotype-environment interaction in Ethiopians.

  Aklillu E, Carrillo JA, Makonnen E, Bertilsson L, Djordjevic N. Aklillu E, et al. Eur J Clin Pharmacol. 2018 Jul;74(7):903-911. doi: 10.1007/s00228-018-2448-y. Epub 2018 Mar 27. Eur J Clin Pharmacol. 2018. PMID: 29589062 Free PMC article.

• The importance of clinical pharmacokinetic-pharmacodynamic studies in unraveling the determinants of early and late tuberculosis outcomes.

  McCallum AD, Sloan DJ. McCallum AD, et al. Int J Pharmacokinet. 2017 Aug;2(3):195-212. doi: 10.4155/ipk-2017-0004. Epub 2017 Jul 12. Int J Pharmacokinet. 2017. PMID: 30283633 Free PMC article. Review.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon

• Other Literature Sources

  • scite Smart Citations