title: miRNA polymorphisms (miR‑146a, miR‑149, miR‑196a2 and miR‑499) are associated with the risk of coronary artery disease.
abstract: Small non‑coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis‑related diseases. However, the effect of miR‑146a, miR‑149, miR‑196a2 and miR‑499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR‑146a, miR‑149, miR‑196a2 and miR‑499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction‑amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR‑149 rs2292832 C>T and miR‑196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR‑146a rs2910164GG genotype was significantly associated with CAD risk in the stent ≥2 group. In addition, miR‑146aG/‑149T/‑196a2C/‑499 G allele combination was significantly associated with CAD prevalence (G‑T‑C‑G and G‑C‑C‑G of miR‑146a/‑149/‑196a2/‑499). The combination genotypes of miR‑146aGG/149TC+CC and miR‑149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR‑146a rs2910164 C>G increased the risk of developing CAD in non‑smoking, hypertensive and nondiabetic subgroups. Furthermore, miR‑149 rs2292832 C>T and miR‑196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR‑149T allele, miR‑196a2C allele and miR‑146aG/‑149T/‑196a2C/‑499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence.
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Sung
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Woo-In
authors.initials: WI
authors.lastname: Yang
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Won-Jang
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Jae-Youn
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: In Jai
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Cha
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Seung-Yun
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 463‑400, Republic of Korea.
authors.forename: Jung Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 463‑400, Republic of Korea.
authors.forename: Kyeong Ah
authors.initials: KA
authors.lastname: Kim
authors.affiliation: Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Ok-Joon
authors.initials: OJ
authors.lastname: Kim
authors.affiliation: Department of Cardiology, CHA Bundang Medical Center, CHA University, Seongnam, Gyeonggi 463‑712, Republic of Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, Gyeonggi 463‑400, Republic of Korea.
authors.forename: Nam-Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D000368:Aged; D000483:Alleles; D015415:Biomarkers; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C542542:MIRN146 microRNA, human; C551557:MIRN149 microRNA, human; C542543:MIRN196 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs