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

摘要

Genetic factors will determine the higher variability, which found in response to lipid reduction treatment (statins). However, due to ethnicity the frequency and effect of single nucleotide polymorphisms (SNPs) may differ. The main aim of lipid lowering medical treatment is to eventually prevent the endogenous production of cholesterol through inhibition of HMG-CoA reductase, The resulting decrease in hepatocyte cholesterol concentration triggers up-regulation of low-density lipoprotein (LDL)-receptor expression by inducing sterol regulatory element-binding protein (SREBP) 2 cleavage, as SREBP-2 activates LDL receptor transcription. The aim of this study was to evaluate the effects of low density lipoprotein receptor (LDL-R) gene variants (rs200727689; rs72658860) in response to atorvastatin treatment in atherosclerotic coronary artery disease (ACAD) in a sample of Iraqi patients. The genetic polymorphisms of rs200727689 and rs72658860 were studied in patients undergoing coronary angiography (CAG). One hundred Iraqi patients include 52 patients treated with 20mg/day and 48 patients treated with 40mg/day, In addition, 100 apparently healthy subjects were genotype for these SNP by the thermal profile of allelic discrimination methods used Real Time PCR (RT-PCR) assay. A significant increase in A allele frequency (rs200727689) compared with controls for total ACAD patients (43% vs 23.5%; OR= 2.46; 95% C.I: 1.60-3.77; p=0.000). For (rs72658860) SNP, among total patients the A allele also increased the frequency substantially compared with the controls (40.5% vs 23.5%; P=0.0003; OR= 2.22; 95% C.I: 1.44 -3.41). In the patients who were treated with atorvastatin, SNP rs72658860 AA genotype significantly affected the response of atorvastatin in dose 20mg compared with 40mg. The result showed in AA genotype of (rs200727689) SNP a reduction in TC concentrations (277.55±108.38 vs 326.99±63.56) and LDL-C concentrations (198.33±100.0 vs 250.01±62.52) in sera compared with GG genotype in patients treated with 20 mg atorvastatin, although, none in all parameters statistically significant differences.