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The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding 期刊论文

编号：

e0af9e3d-e0e3-4c32-875d-9a426568fa0e
作者：

Wu, C.^[1,2] Gong, Y.^[3] Sun, A.^[1,2] Zhang, Y.^[1,2] Zhang, C.^[1,2] Zhang, W.^[1,2] Zhao, G.^[1,2] Zou, Y.^[1,2] Ge, J.^[1,2]
语种：

English
期刊：

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES ISSN：0939-4753 2013 年 23 卷 7 期 (693 - 698) ; JUL
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关键词：

Coronary heart disease MTHFR Association study microRNA polymorphism
摘要：

Background and aims: Abnormal functioning of 5,10-methylenetetrahydrofolate reductase (MTHFR) enhances the risk for coronary heart disease (CHD). Here, we tested whether a single-nucleotide polymorphism (SNP) located in the 3' untranslated region (UTR) of MTHFR was associated with CHD susceptibility by affecting microRNAs binding. Methods and results: We first analyzed in silico the SNPs localized in the 3' UTR of MTHFR for their ability to modify miRNA binding. We observed that rs4846049 (G>T) was a potential candidate SNP to modulate miRNAs: MTHFR mRNA complex, with the greatest changed binding free energy for has-miR-149. Based on luciferase analysis, hsa-miR-149 inhibited the activity of the reporter vector carrying -T allele, but not -G allele. We further conducted a case-control study (654 vs 455) in a Chinese Han population. rs4846049 was significantly associated with increased risk for CHD. In addition, the Tallele was associated with decreased levels of HDL-cholesterol and apoA. Finally, we observed a reduced MTHFR protein level in peripheral blood mononuclear cells of CHD patients with TT carriers compared to GG carriers of rs4846049. Conclusion: Our results suggest that rs4846049 (G>T) of MTHFR is associated with increased risk for CHD. We also identified a potentially pathogenetic mechanism of SNP-modified posttranscriptional gene regulation by miRNAs to MTHFR. (C) 2012 Elsevier B.V. All rights reserved.
推荐引用方式
GB/T 7714：

Wu C.,Gong Y.,Sun A., et al. The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding [J].NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES,2013,23(7):693-698.
APA：

Wu C.,Gong Y.,Sun A.,Zhang Y.,&Ge J..(2013).The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding .NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES,23(7):693-698.
MLA：

Wu C., et al. "The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding" .NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES 23,7(2013):693-698.

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