TY - JOUR
T1 - A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression
AU - Xiong, Xing dong
AU - Cho, Miook
AU - Cai, Xiu ping
AU - Cheng, Jie
AU - Jing, Xia
AU - Cen, Jin ming
AU - Liu, Xinguang
AU - Yang, Xi li
AU - Suh, Yousin
N1 - Funding Information:
The study was supported by grants from the National Natural Science Foundation of China ( 81000143 , 81370456 ), the Natural Science Foundation of Guangdong Province ( S2012010008219 , S2011010002922 ), the Medical Scientific Research Foundation of Guangdong Province ( B2009191 , A2011431 ), the Science and Technological Program for Dongguan′s Higher Education, Science and Research, and Health Care Institutions ( 2011105102007 , 200910815256 ), the Guangdong University Students Innovative Pilot Program ( KY1232 , 1057113012 , ZZDC006 ) and the Science & Technology Innovation Fund of Guangdong Medical College ( STIF201102 ).
PY - 2014/3
Y1 - 2014/3
N2 - miRNAs are small non-coding RNAs that play an important role in numerous physiological processes. Common single nucleotide polymorphisms (SNPs) in pre-miRNAs may change their property through altering miRNAs expression and/or maturation, resulting in diverse functional consequences. To date, the role of genetic variants in pre-miRNAs on coronary artery disease (CAD) risk remains poorly understood. Here we aimed to evaluate the influence of three common SNPs in pre-miRNAs (miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, miR-499 rs3746444 T>C) on individual susceptibility to CAD in a Chinese population of 295 CAD patients and 283 controls. Genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. In a logistic regression analysis, we detected an association of rs2910164 in pre-miR-146a with the CAD risk; compared with the GG homozygotes, the GC heterozygotes [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.06-3.36, P=0.029] and the CC homozygotes (OR=1.83, 95% CI=1.01-3.32, P=0.046) genotype were statistically significantly associated with the increased risk for CADs. As we used further genotype association models, we found a similar trend of the association in recessive model (OR=1.86, 95% CI=1.09-3.19, P=0.023). We also found that the genotypes of miR-146a rs2910164 were associated with its mature miRNA expression by analyzing 23 PBMC samples from CAD patients. Individuals carrying rs11614913 GC or CC genotypes showed 3.2-fold higher expression compared to GG genotype carriers (P<. 0.05). We observed no association of the other two SNPs in miR-196a2 (rs11614913) and miR-499 (rs3746444) with the CAD incidence. Our data provide the first evidence that the miR-146a rs2910164 polymorphism is associated with increased risk of CAD in Chinese Han population, which may be through influencing the expression levels of the miRNA.
AB - miRNAs are small non-coding RNAs that play an important role in numerous physiological processes. Common single nucleotide polymorphisms (SNPs) in pre-miRNAs may change their property through altering miRNAs expression and/or maturation, resulting in diverse functional consequences. To date, the role of genetic variants in pre-miRNAs on coronary artery disease (CAD) risk remains poorly understood. Here we aimed to evaluate the influence of three common SNPs in pre-miRNAs (miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, miR-499 rs3746444 T>C) on individual susceptibility to CAD in a Chinese population of 295 CAD patients and 283 controls. Genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. In a logistic regression analysis, we detected an association of rs2910164 in pre-miR-146a with the CAD risk; compared with the GG homozygotes, the GC heterozygotes [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.06-3.36, P=0.029] and the CC homozygotes (OR=1.83, 95% CI=1.01-3.32, P=0.046) genotype were statistically significantly associated with the increased risk for CADs. As we used further genotype association models, we found a similar trend of the association in recessive model (OR=1.86, 95% CI=1.09-3.19, P=0.023). We also found that the genotypes of miR-146a rs2910164 were associated with its mature miRNA expression by analyzing 23 PBMC samples from CAD patients. Individuals carrying rs11614913 GC or CC genotypes showed 3.2-fold higher expression compared to GG genotype carriers (P<. 0.05). We observed no association of the other two SNPs in miR-196a2 (rs11614913) and miR-499 (rs3746444) with the CAD incidence. Our data provide the first evidence that the miR-146a rs2910164 polymorphism is associated with increased risk of CAD in Chinese Han population, which may be through influencing the expression levels of the miRNA.
KW - Coronary artery disease
KW - MicroRNA
KW - Risk
KW - Single nucleotide polymorphism
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U2 - 10.1016/j.mrfmmm.2014.01.001
DO - 10.1016/j.mrfmmm.2014.01.001
M3 - Article
C2 - 24447667
AN - SCOPUS:84895877814
SN - 0027-5107
VL - 761
SP - 15
EP - 20
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
ER -