Prevalence of protective haplotypes of the SLCO1B1 gene for statin transport in Mexican populations
Abstract
Aim: To evaluate the genetic distribution of the rs4149056 and rs2306283 variants in the SLCO1B1 gene in Mexican Mestizo (admixed) and Native American groups. Materials & methods: We recruited 360 volunteers who were qPCR-genotyped with TaqMan probes. Results: Allele and genotype frequencies are reported. Among the expected rs4149056–rs2306283 haplotypes, T–A (42.35–58.47%) was the most prevalent which relates to the normal activity of the OATP1B1 transporter. This was followed by the T–G haplotype associated with further statin transport and cholesterol reduction (32.49–43.76%). Conclusion: Based on these SLCO1B1 gene variants, we confirmed that a minimum fraction of the Mexican study populations would be at risk from decreasing simvastatin transport and the development of statin-induced myopathy.
Lay abstract
The clinical response to statins, mainly atorvastatin and simvastatin, can be modified by interindividual variability including variations in the SLCO1B1 gene. This gene, that encodes the statin transporter OATP1B1, helps to regulate the cholesterol levels in the blood and is responsible for the presence of adverse drug reactions related to the statin consumption, such as muscular sickness. This study analyzes the distribution of the SLCO1B1 gene variants rs4149056 and rs2306283 in geographically dispersed samples of the two main populations in Mexico: two Mestizo (admixed) populations and three Native American groups. We found that the genetic combinations of T–A and T–G for the two SLCO1B1 gene variants – associated with normal or efficient activity of the transporter OATP1B – were predominant in all of the study population. Therefore, the SLCO1B1 gene variability suggests that a majority of the Mexican population will respond favorably to simvastatin and have a low risk of developing associated muscular complications.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians. Basic Clin. Pharmacol. Toxicol. 110(5), 460–468 (2012).
- 2. Possible gene-gender interaction between the SLCO1B1 polymorphism and statin treatment efficacy. Neuro. Endocrinol. Lett. 33(2), 22–25 (2012).
- 3. . Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol. Rev. 63(1), 157–181 (2011). •• Provides a general and specific molecular overview of the OATP1B1 transporter, as well as its implication in pharmacogenetics and drug interactions.
- 4. SLCO1B1 genetic variants, long-term low-density lipoprotein cholesterol levels and clinical events in patients following cardiac catheterization. Pharmacogenomics 16(5), 449–458 (2015).
- 5. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin. Pharmacol. Ther. 96(4), 423–428 (2014). • Update to the 2012 Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin. Provides therapeutic suggestions for simvastatin administration based on SLCO1B1 genotype.
- 6. SLCO1B1 c.388A>G polymorphism is associated with HDL-C levels in response to atorvastatin in Chilean individuals. Int. J. Mol. Sci. 16(9), 20609–20619 (2015).
- 7. Pharmacogenetics of OATP transporters reveals that SLCO1B1 c.388A>G variant is determinant of increased atorvastatin response. Int. J. Mol. Sci. 12(9), 5815–5827 (2011).
- 8. The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin. Pharmacol. Ther. 92(1), 112–117 (2012). • Describes – for the first time – clinical guidelines to be followed to prescribe simvastatin based on the association of the SLCO1B1 genotype with clinical response.
- 9. A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers. BMC Cancer 16, 74 (2016). • Demonstrates the SLCO1B1, MTHFR, DRD3 and MDR1 genotype–phenotype relationship for atorvastatin in a Mexican population.
- 10. SLCO1B1 rs4149056 polymorphism associated with statin-induced myopathy is differently distributed according to ethnicity in the Brazilian general population: amerindians as a high risk ethnic group. BMC Med. Genet. 12, 136 (2011).
- 11. Genetic data of 15 autosomal STRs (Identifiler kit) of three Mexican Mestizo population samples from the states of Jalisco (West), Puebla (Center), and Yucatan (Southeast). Forensic Sci. Int. Genet. 3(3), e71–e76 (2009).
- 12. Importance of the geographic barriers to promote gene drift and avoid pre- and post-Columbian gene flow in Mexican native groups: evidence from forensic STR loci. Am. J. Phys. Anthropol. 160(2), 298–316 (2016).
- 13. . GenAlEx 6.5: genetic analysis in Excel. Population genetic software for teaching and research – an update. Bioinformatics 28(19), 2537–2739 (2012).
- 14. . Arlequin ver. 3.0: an integrated software package for population genetics data analysis. Evol. Bioinform. Online 1, 47–50 (2005).
- 15. SNPAnalyzer 2.0: a web-based integrated workbench for linkage disequilibrium analysis and association analysis. BMC Bioinformatics 9, 290 (2008).
- 16. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344(6189), 1280–1285 (2014). •• In this genomic study, ancestral patterns are described in both Mexican Mestizo (admixed) and Native American populations, which can explain differences in disease distribution and clinical responses throughout this country.
- 17. Population pharmacogenomics for precision public health in Colombia. Front. Genet. 10, 241 (2019).
- 18. Projected impact of a multigene pharmacogenetic test to optimize medication prescribing in cardiovascular patients. Pharmacogenomics 19(9), 771–782 (2018). • This work shows the clinical relevance of a multigenic pharmacogenetic test to support personalized clinical decisions based on interindividual variability.
- 19. Genetic variability among Mexican Mestizo and Amerindian populations based on three ABCB1 polymorphisms. Mol. Biol. Rep. 45(6), 2525–2533 (2018).
- 20. Contrasting patterns of Nuclear and mtDNA diversity in Native American populations. Ann. Hum. Genet. 74, 525–538 (2010).
- 21. Effects of delivering SLCO1B1 pharmacogenetic information in randomized trial and observational settings. Circ. Genom. Precis. Med. 11(9), e002228 (2018).
- 22. Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment. Drug Saf. 33(3), 171–187 (2010).
