| Objective:Atherosclerosis (AS) is regarded as the major causes of disability and death in diabetic patients. However, the precise pathogenesis of atherosclerosis is not entirely clear. Recently genome-wide association studies (GWAS) have revealed atherosclerosis is related with some epigenetic genes. The study intends to investigate the possible association of miR-146a and transcriptional coactivator p300 polymorphisms with carotid atherosclerosis in type 2 diabetes mellitus.Method:The study group included 379 type 2 diabetes mellitus patients without carotid atherosclerosis and 596 type 2 diabetes mellitus patients with carotid atherosclerosis from the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, China between March 2013 and December 2014. Genotyping of miR-146a and p300 polymorphism was performed using an allelic discrimination assay with TaqMan-MGB probes. Statistical analysis was conducted to figure out the risk factors of carotid atherosclerosis in type 2 diabetes.Results:①In miR-146a gene, genotype frequencies of GG, GC and CC were 14.87%,47.18% and 37.95%. In p300 gene, genotype frequencies of AA, AG and GG were 84.82%,14.36% and 0.82%. The distribution of genotype frequencies of miR-146a and p300 gene polymorphisms comply with the Hardy-Weinberg equilibrium. ② The CC genotype of rs2910164 within miR-146a is associated with an increased risk of carotid vulnerable plaque in the Chinese type 2 diabetes mellitus patients, but this association was not found in type 2 diabetes mellitus with carotid atherosclerosis and plaque load groups. In addition, no statistically significant difference in transcriptional coactivator p300 genotypes distribution was observed between the type 2 diabetes mellitus with and without carotid atherosclerosis group, plaque stability and plaque load, respectively. ③In the stratified analyses, this study found that the risk of miR-146aCC genotype increase vulnerable plaque was more pronounced in subjects older, females, subjects with more than 10 years diabetes duration, and subjects with hypertension. ④The research further analyzed gene-gene interaction between miR-146a rs2910164 and p300 rs20551 polymorphisms, but there isn’t possible joint effect between the two genes in enhancing the risk of carotid atherosclerosis, plaque stability, and plaque load.Conclusion:The miR-146a rs2910164 polymorphism might be associated with carotid vulnerable plaque risk in the Chinese type 2 diabetes mellitus patients, particularly among older, females and subjects with more than 10 years diabetes duration and hypertension. The transcriptional coactivator p300 rs20551 polymorphism may not be a risk factor for the development of atherosclerosis and vulnerable plaques in type 2 diabetes mellitus. |
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