期刊
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
卷 23, 期 7, 页码 693-698出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.numecd.2012.02.009
关键词
Coronary heart disease; MTHFR; Association study; microRNA; polymorphism
资金
- National Natural Science Foundation of China [30725036]
- National Basic Research Program of China [2011CB503905]
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.
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