Search

Atherosclerosis and its cardiovascular complications are the main cause of death in diabetic patients. Patients with diabetes mellitus have a greater than 10-fold risk of cardiovascular disease in their lifetime. The carotid Intima-Media Thickness (cIMT), a surrogate marker for the presence and progression of atherosclerosis, predicts future cardiovascular events in asymptomatic subjects with Type 2 Diabetes Mellitus (T2DM). This review focuses on genetic variants that contribute to the pathobiology of subclinical atherosclerosis in the setting of T2DM. Specifically, we devoted our attention to wellstudied genes selected for their relevance for atherosclerosis. These include: The Renin-Angiotensin- Aldosterone System (RAAS), Apolipoprotein E (ApoE), Methylenetetrahydrofolate Reductase (MTHFR) and pro-inflammatory genes. The ever-growing availability of advanced genotyping technologies has made Genome-Wide Association Studies (GWAS) possible. Although several bioinformatics tools have been developed to manage and interpret the huge amounts of data produced, there has been limited success in the many attempts to uncover the biological meaning of the novel susceptibility loci for atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor κB ligand/receptor-activator of nuclear factor κB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM)., Patients and Methods: 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA., Results: Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22-5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques., Conclusions: Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.