Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response

Abstract

Objective: Using candidate gene approach, we have investigated the effect of single nucleotide polymorphism (SNP) in genes related to lipid metabolism and atherosclerosis on dyslipidemia and atorvastatin response. Methods: The study included 157 patients treated with atorvastatin and 145 controls. Genomic DNA was isolated and genotyped using SNPlex technology. Results: Allele and genotype disease association test revealed that APOB rs693 (OR: 2.2 [1.5-3.2], p = 0.0001) and CD36 rs1984112 (OR: 3.7 [1.9-7.0], p = 0.0002) SNPs were independent risk factors for hypercholesterolemia. Only APOB rs693 T variant allele was associated with increased LDL cholesterol levels (> 160 mg/dL). After atorvastatin treatment (10 mg/day/4 weeks), LIPC - 514T allele was positively associated with LDL cholesterol reduction. Conclusion: The current study reinforces the current knowledge that carrying APOB rs693 is an independent risk factor for dyslipidemia and higher LDL levels. Furthermore, we found that a variant of CD36 was associated with dyslipidemia as a risk (rs1984112) factor. Finally, atorvastatin response could be predicted by LIPC - 514C>T SNP and physical activity. In conclusion, our data evidences the contribution of genetic markers and their interaction with environmental factor in the variability of statin response.