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.

The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients

“…After treatment with simvastatin, we found that APOE2 and APOE3 carriers had greater TC and LDL-C reduction compared to APOE4 carriers. Our findings were in agreement with several studies 9,11,12,35,36 in which APOE2 carriers had a greater response but APOE4 carriers had a poorer response to statin therapy. The T A B L E 3 Relationship of APOE polymorphism with serum lipids in hypercholesterolemic patients, before and after simvastatin treatment mechanism of APOE that influences lipid levels after statin therapy may be due to the affinity binding to low-density lipoprotein receptors (LDLR).…”

“…8 Apolipoprotein E (APOE), cholesteryl ester transfer protein (CETP), and proprotein convertase subtilisin kexin type 9 (PCSK9) are the genes in lipid metabolism that were studied, specifically the effect on the response to statin therapy in various populations. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Nevertheless, the results on statin response according to these polymorphisms were inconsistent among the various populations. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Moreover, data on the effect of these polymorphisms on statin response in Thai hypercholesterolemic patients are rare.…”

Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels

“…This receptor is a 160-KDa transmembrane glycoprotein, ubiquitously distributed and encoded by LDLR gene located in chromosome 19, which spans 45 Kb and contains 18 exons encoding for six functional domains in the mature protein. 11,12 Moreover, no association was found between LDLR rs5925 genetic variant and atorvastatin response in Chilean Amerindian subjects, 13 suggesting that LDLR polymorphism can influence plasma lipid levels and account for CVD risk, but that effect could also be partially influenced by ethnical characteristics in the studied individuals. 6 In this study, we evaluated LDLR rs5925 (1959C > T or AvaII) genetic variant, previously reported to be associated with increased total cholesterol (TC) and LDL-C in Chinese, Brazilian, Hispanic, and non-Hispanic white individuals.…”

“…Amerindian subjects, 13 suggesting that LDLR polymorphism can influence plasma lipid levels and account for CVD risk, but that effect could also be partially influenced by ethnical characteristics in the studied individuals.…”

A Study to Explore the LDLR Gene Polymorphisms Contribute to Atorvastatin Response in a Sample of Iraqi Population with Atherosclerotic Coronary Artery Disease

“…Atorvastatin controls elevated levels of cholesterol and reduces the risk of heart disease; therefore, studying the association between susceptible gene polymorphism and lipid-reducing efficacy is a great benefit to the clinical application of atorvastatin [12]. Recently, a major focus has been on the genetic factor as a major contributor to a drug response, but a continuum of different responses across treated persons has appeared when an equivalent dosage is used [13]. Atorvastatin is one of those whose drug effectiveness is affected by both genetic and environmental factors.…”