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.
Background. The TYMS gene contains one of the 68 very important polymorphisms because affect the expression level of the thymidylate synthetase (TS), such as TSER that is involved in the toxicity and therapeutic response to 5'-Fluoracil (5’-FU), the drug of choice for different cancers. However, the inclusion of additional TYMS variants have improved the association with the expression levels. Although the TSER variants have been studied in the Mexican population, genotypes including the G>C SNP in the TYMS gene are completely unknown in this country. Methods and results. A Mexican population sample (n= 156) was genotyped for the TSER and G>C polymorphisms by PCR and PCR-RFLPs followed by PAGE and silver staining, respectively. Allele and genotype frequencies were estimated, and Hardy-Weinberg equilibrium was demonstrated for both TYMS variants in the studied population sample. For TSER, the most frequent allele was 2R (52.56%), as well as the genotype 2R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution (FST-value=0.01564; P-value=0.0000). When the G>C variant was included, a high frequency of the genotypes 2RG/2RG, 2RG/3RC, and 3RC/3RC was observed (84.6%). This finding allows predicting a high frequency of low expression for the thymidylate synthase (TS) in the Mexican population, which can predispose to peculiar treatment responses of 5´-FU, methotrexate, and pemetrexed. Conclusion. This study justifies obtaining the pharmacogenetic profile of TYMS variants in candidate Ca patients for 5´-FU treatment, given the high frequency of low TS expression in the Mexican population.
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