Lagos Jenny, Zambrano Tomás, Rosales Alexy, Salazar Luis A
Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera (BIOREN-UFRO), Av. Francisco Salazar 01145, 4811230 Temuco, Chile.
Int J Mol Sci. 2015 Apr 9;16(4):7890-9. doi: 10.3390/ijms16047890.
Genetic factors can determine the high variability observed in response to lipid-lowering therapy with statins. Nonetheless, the frequency of single nucleotide polymorphisms (SNPs) and their impact can vary due to ethnicity. Because the Chilean population carries a strong Amerindian background, the objective of this study was to evaluate the influence of apolipoprotein E (APOE) variants (rs429358, rs7412) and the 1959C>T SNP (rs5925) in the low-density lipoprotein receptor (LDLR) in response to atorvastatin treatment in hypercholesterolemic individuals. A hundred and thirty nine subjects undergoing statin therapy were included. Identification of Amerindian mtDNA haplogroups was determined by polymerase chain reaction (PCR) and PCR followed by restriction fragment length polymorphism (RFLP), respectively. SNPs were determined by PCR-RFLP. Out of the 139 individuals studied, 84.4% had an Amerindian background, according to mtDNA analysis. In relation to APOE variants, carriers of the E3/4 genotype presented lower cholesterol reduction compared to genotype E3/3 (LDL-C: -18% vs. -29%, p ˂ 0.001). On the other hand, the LDLR rs5925 SNP was not related to atorvastatin response (p = 0.5760). Our results suggest that APOE SNPs are potential predictors to atorvastatin therapy in Amerindian Chilean subjects.
遗传因素可决定他汀类药物降脂治疗中观察到的高变异性。尽管如此，单核苷酸多态性（SNP）的频率及其影响可能因种族而异。由于智利人群具有强烈的美洲印第安人背景，本研究的目的是评估载脂蛋白E（APOE）变体（rs429358、rs7412）和低密度脂蛋白受体（LDLR）中的1959C>T SNP（rs5925）对高胆固醇血症个体阿托伐他汀治疗反应的影响。纳入了139名接受他汀类药物治疗的受试者。分别通过聚合酶链反应（PCR）和PCR后接限制性片段长度多态性（RFLP）来确定美洲印第安人线粒体DNA单倍群。通过PCR-RFLP确定SNP。根据线粒体DNA分析，在139名研究对象中，84.4%具有美洲印第安人背景。关于APOE变体，与E3/3基因型相比，E3/4基因型携带者的胆固醇降低幅度较小（LDL-C：-18%对-29%，p＜0.001）。另一方面，LDLR rs5925 SNP与阿托伐他汀反应无关（p = 0.5760）。我们的结果表明，APOE SNP是智利美洲印第安人受试者阿托伐他汀治疗的潜在预测指标。
