The Association of 3-Hydroxy-3-Methylglutaryl-CoA Reductase, Apolipoprotein E, and Solute Carrier Organic Anion Genetic Variants with Atorvastatin Response among Jordanian Patients with Type 2 Diabetes.

Atorvastatin is commonly used among type 2 diabetic (DM2) patients at the University of Jordan Hospital to prevent cardiovascular complication. However, we noticed that there is a wide inter-individual variation in the efficacy and toxicity of atorvastatin. This study aimed to find out the effects of major genetic variants in 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), Apolipoprotein E (APOE), and Solute Carrier Organic Anion (SLCO1B1) genes on atorvastatin response among DM2 patients. A sample of 139 DM2 patients on 20 mg of atorvastatin was included in this study. The lipid and glycemic profile and the levels of hepatic enzymes alanine aminotransferase (ALT) and aspartate transaminase were recorded before and after 3 months of atorvastatin treatment. Additionally, the genetic variants and and and were genotyped using an Applied Biosystems DNA sequencing method (ABI3730×1). We found that atorvastatin reduced total cholesterol and low-density lipoprotein (LDL) more significantly (-value < 0.05) in patients with wild genotype than variant alleles and . Furthermore, the ALT level was elevated significantly (-value < 0.05) by 27% in patients with heterozygous G/A genotype, while it was not elevated among wild genotype carriers. Additionally, atorvastatin reduced total cholesterol more significantly (-value < 0.05) in patients with and haplotypes and increased ALT levels by 27% (-value < 0.05) in patients with and haplotypes. In conclusion, it was found in this study that and genotypes can be considered as potential genetic biomarkers of atorvastatin response among DM2 patients of Jordanian Arabic origin. Further clinical studies with larger sample numbers are needed to confirm these findings.