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.

Keywords::

• Mexicans
• OATP1B1
• rs2306283
• rs4149056
• SLCO1B1
• SLCO1B1*1B
• SLCO1B1*5

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/pme-2020-0172

Author contributions

Conceived and designed the experiments: AF Favela-Mendoza, H Rangel-Villalobos. Performed the experiments: BG Rodríguez-Rodríguez, M Chávez-Arreguin, E Rojas-Prado. Analyzed the data: BG Rodríguez-Rodríguez, JA Aguilar-Velázquez, AF Favela-Mendoza. Contributed reagents/materials/analysis tools: AF Favela-Mendoza, G Martínez-Cortés, H Rangel-Villalobos. Wrote the paper: AF Favela-Mendoza, BG Rodríguez-Rodríguez, H Rangel-Villalobos. Population sampling and DNA extraction process: BG Rodríguez-Rodríguez, M Chávez-Arreguin.

Acknowledgments

The authors would like to thank the volunteers who participated in this study.

Financial & competing interests disclosure

University of Guadalajara provided institutional support to the authors (grant no. PRO-SNI 2019). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

English language support was provided by Scribendi and was funded by Universidad de Guadalajara PRO-SNI 2019.

Ethical conduct of research

All individuals signed a written informed consent, according to the ethical guidelines of the Helsinki Declaration. Before population sampling, ethical approval was obtained from the Committee of Ethics and Research of the Centro Universitario de la Ciénega of the Universidad de Guadalajara (CUCI-UdeG, Mexico). The anonymity of the recruited individuals was preserved at all time.

Additional information

Funding

University of Guadalajara provided institutional support to the authors (grant no. PRO-SNI 2019). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. English language support was provided by Scribendi and was funded by Universidad de Guadalajara PRO-SNI 2019.