Polymorphism AvaII of the LDL receptor (rs5925) is associated with carotid-intima media thickness in patients with diabetes mellitus type 2

Abstract

Introduction Increased serum level of low density lipoprotein (LDL) cholesterol is a well established risk factor for atherosclerosis development and progression. Genetic variation in the LDL receptor gene could modulate serum LDL level and response to statin treatment thus affecting atherosclerosis development and progression. The present study was designed to investigate the association between polymorphism AvaII (rs5925) of the LDL receptor gene with serum lipid levels and carotid intima-media thickness (CIMT) in patients with diabetes mellitus type 2 (DM2).Methods 595 patients with DM2 (399 on statin therapy and 196 without) were enrolled in the study. The carotid intima-media thickness was assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. AvaII (rs5925) genotypes were determined by real-time PCR. Results Genotype distribution and allele frequencies were not statistically significantly different between DM2 patients with regard to statin therapy. In DM2 patients using statins the highest serum levels of total and LDL cholesterol were observed in homozygous carriers of the A+ allele. After adjustment for well established cardiovascular risk factors homozygosity for the A+ allele (β=0.441 and p=0.04), statin treatment as well as serum levels of HDL, triglycerides, hsCRP and fibrinogen were independently associated with CIMT. Interactions of AvaII genotypes A-A+ and A+A+ with statin treatment were not statistically significant.Conclusion Homozigosity for the A+ allele of the AvaII polymorphism is associated with greater CIMT in DM2 patients.

Keywords

• atherosclerosis, diabetes mellitus type 2, carotid intima-media thickness, LDL receptor, polymorphism
• farmakogenetika