Genetic biomarkers of atorvastatin efficacy in Chilean subjects with Amerindian background

Abstract

Background: Lipid-lowering response after statin therapy presents high variability between individuals, which has been attributed to factors as gender, ethnicity and genetic variants, including single nucleotide polymorphisms in cholesterol metabolism related genes. Thus, the aim of the present study was to evaluate the influence of genetic variants of APOE (rs429358 and rs7412), SREBP-2 (rs4822063), SCAP (rs12487736) and LDLR (c.1959C>T) on lipid-lowering response to atorvastatin in Amerindian Chilean subjects with hypercholesterolemia (HC). Design(s): A total of 138 HC individuals were included in this study. Serum cholesterol levels were determined before and after of atorvastatin treatment (10 mg/day/4 weeks). Genotyping of the studied polymorphisms and ethnic characterization through Amerindian haplogroups (A, B, C and D) of mithocondrial DNA was achieved by PCR and PCR-RFLP, respectively. Result(s): Respect to the ethnical characterization, 84% of total individuals was classified as Amerindian. No association between Amerindian haplogroups and lipid-lowering response was observed. The APOE polymorphism analysis showed a less cholesterol reduction in individuals carrying the E3/4 genotype in comparison with E3/3 homozygote individuals (Total cholesterol: 21% vs. 12%, p<0.001; LDL-cholesterol: 29% vs. 18%, p<0.001). Similarly, the presence of C allele (rs4822063) at the SREBP-2 was associated with less reduction of total cholesterol (26% vs. 17%, p= 0.015) and LDL cholesterol levels (38% vs. 24%, p=0.013). No differences were observed in atorvastatin response among variants of SCAP and LDLR. Conclusion(s): Were identified two genetic variants as potential biomarkers of less atorvastatin efficacy in Amerindian HC subjects, which can explain partially the high variability of response to statin therapy in Chilean population.