The relationship of miR-146a gene polymorphism with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus.
OBJECTIVE
Atherosclerosis (AS) is regarded as the major cause of disability and death in diabetic patients. However, its precise pathogenesis is not entirely clear. Recent genome-wide association studies (GWAS) have revealed AS is related to some epigenetic changes. This study aimed to investigate the possible associations of miR-146a and transcriptional coactivator p300 polymorphisms with carotid atherosclerosis in type 2 diabetes mellitus.


METHODS
This case-control study included 596 type 2 diabetes mellitus patients with carotid atherosclerosis and 379 patients without carotid atherosclerosis. Genotyping of miR-146a and p300 polymorphisms was performed by allelic discrimination assay with TaqMan-MGB probes.


RESULTS
The CC genotype of rs2910164 in miR-146a was found to be associated with an increased risk of carotid vulnerable plaque in the Chinese type 2 diabetes mellitus patients, but this association was not found in the type 2 diabetes mellitus patients with carotid atherosclerosis or in the plaque load group. In addition, no significant difference in transcriptional coactivator p300 genotype distribution was observed between the type 2 diabetes mellitus patients with and without carotid atherosclerosis, plaque stability or plaque load, respectively. Stratified analyses revealed that the miR-146aCC genotype was associated with an increased risk of vulnerable plaque in subjects who were older, females, those with diabetes duration of more than 10 years, and those with hypertension. The gene-gene interactions between the miR-146a rs2910164 and p300 rs20551 polymorphisms were further analysed, but no combined effects of these two genes on enhancing the risk of carotid atherosclerosis, plaque stability, or plaque load were detected.


CONCLUSIONS
The miR-146a rs2910164 polymorphism might be associated with carotid vulnerable plaque risk in Chinese type 2 diabetes mellitus patients, particularly in older patients, females, those with diabetes duration of more than 10 years and those with hypertension. The transcriptional coactivator p300 rs20551 polymorphism may not be a risk factor for the development or progression of atherosclerosis in type 2 diabetes mellitus.
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Jing
J
Shen
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Min
M
Zhang
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Mingfang
M
Sun
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Kang
K
Tang
Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China. Electronic address: zhoubo915@126.com.
Bo
B
Zhou
D000368:Aged; D044466:Asian People / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C542542:MIRN146 microRNA, human; D035683:MicroRNAs
Atherosclerosis; Single nucleotide polymorphism; Type 2 diabetes mellitus; miR-146a gene; p300 gene