Association of miR-196a2, miR-27a, and miR-499 polymorphisms with isolated congenital heart disease in a Chinese population.
We hypothesized that single nucleotide polymorphisms (SNPs) in certain microRNAs contribute to congenital heart disease (CHD) phenotypes. Five hundred and seventy-three subjects were enrolled in this study. DNA extracted from peripheral blood cells was used for SNP genotyping of miR-196a2 (rs11614913), miR-27a (rs11671784, rs895819), and miR-499 (rs3746444). Allele and genotype association analyses were performed to evaluate the correlation between certain microRNA SNPs and three phenotypes of isolated CHD: atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA). All the participants carried a homozygous CC variant of miR-27a (rs11671784). The homozygous CC variant of miR-196a2 (rs11614913, T>C) was negatively associated with ASD compared with the wild-type TT variant (OR = 0.379, 95%CI = 0.209-0.686, P = 0.001). The miR-196a2 C allele was negatively associated with ASD compared with the T allele (OR = 0.646, 95%CI = 0.491-0.849, P = 0.002). The statistically significant results were further confirmed by dominant and recessive model assays. SNPs of miR-27a (rs895819, T>C) and miR-499 (rs3746444, A>G) showed diverse association with ASD, VSD, or PDA, but the differences were not statistically significant. The rs11614913 (T>C) SNP of miR-196a2 is associated with ASD, and the homozygous CC variant and the C allele are protective factors associated with ASD. The homozygous CC variant and the C allele of the rs11614913 (T>C) SNP of miR-196a2 are associated with a significantly reduced risk of ASD.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.|Department of Cardiology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
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K
Yu
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
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Y
Ji
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
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H
Wang
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
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QK
Xuan
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
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BB
Li
Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, ; Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China.
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Xiao
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China huaianyk@163.com.
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Sun
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China huaianyk@163.com.
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Kong
D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C542543:MIRN196 microRNA, human; C531388:MIRN27 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs