title: APOE polymorphisms contribute to reduced atorvastatin response in Chilean Amerindian subjects.
abstract: 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.
authors: 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. tm.jenny.lagos@gmail.com.
authors: Jenny
authors: J
authors: Lagos
authors: 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. t.andreszambrano@gmail.com.
authors: Tomás
authors: T
authors: Zambrano
authors: 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. tm.arosales@gmail.com.
authors: Alexy
authors: A
authors: Rosales
authors: 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. luis.salazar@ufrontera.cl.
authors: Luis A
authors: LA
authors: Salazar
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics*; D000069059:Atorvastatin / Q000627:therapeutic use*; D002677:Chile; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D004272:DNA, Mitochondrial; C573412:LDLR protein, human; D011973:Receptors, LDL; D000069059:Atorvastatin