Mamasoula Chrysovalanto, Prentice R Reid, Pierscionek Tomasz, Pangilinan Faith, Mills James L, Druschel Charlotte, Pass Kenneth, Russell Mark W, Hall Darroch, Töpf Ana, Brown Danielle L, Zelenika Diana, Bentham Jamie, Cosgrove Catherine, Bhattacharya Shoumo, Riveron Javier Granados, Setchfield Kerry, Brook J David, Bu'Lock Frances A, Thornborough Chris, Rahman Thahira J, Doza Julian Palomino, Tan Huay L, O'Sullivan John, Stuart A Graham, Blue Gillian, Winlaw David, Postma Alex V, Mulder Barbara J M, Zwinderman Aelko H, van Engelen Klaartje, Moorman Antoon F M, Rauch Anita, Gewillig Marc, Breckpot Jeroen, Devriendt Koen, Lathrop G Mark, Farrall Martin, Goodship Judith A, Cordell Heather J, Brody Lawrence C, Keavney Bernard D
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Circ Cardiovasc Genet. 2013 Aug;6(4):347-53. doi: 10.1161/CIRCGENETICS.113.000191. Epub 2013 Jul 22.
Association between the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is contentious.
We compared genotypes between CHD cases and controls and between mothers of CHD cases and controls. We placed our results in context by conducting meta-analyses of previously published studies. Among 5814 cases with primary genotype data and 10 056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (odds ratio [OR], 0.96 [95% confidence interval, 0.87-1.07]). A random-effects meta-analysis of all studies (involving 7697 cases and 13 125 controls) suggested the presence of association (OR, 1.25 [95% confidence interval, 1.03-1.51]; P=0.022) but with substantial heterogeneity among contributing studies (I(2)=64.4%) and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR <0.05), which together contributed 83% of all cases, yielded no evidence of association (OR, 0.97 [95% confidence interval, 0.91-1.03]) without significant heterogeneity (I(2)=0). Moreover, meta-analysis of 1781 mothers of CHD cases (829 of whom were genotyped in this study) and 19 861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR, 1.13 [95% confidence interval, 0.87-1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate.
The MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.
亚甲基四氢叶酸还原酶（MTHFR）基因的C677T多态性与先天性心脏病（CHD）之间的关联存在争议。
我们比较了CHD病例与对照以及CHD病例母亲与对照之间的基因型。我们通过对先前发表的研究进行荟萃分析来阐述我们的结果。在5814例有原始基因型数据的病例和10056例对照中，没有证据表明MTHFR C677T基因型与CHD风险之间存在关联（优势比[OR]，0.96[95%置信区间，0.87 - 1.07]）。对所有研究（涉及7697例病例和13125例对照）进行的随机效应荟萃分析表明存在关联（OR，1.25[95%置信区间，1.03 - 1.51]；P = 0.022），但纳入研究之间存在显著异质性（I² = 64.4%）以及存在发表偏倚的证据。仅对大型研究（定义为对数OR的方差<0.05）进行荟萃分析，这些大型研究共占所有病例的83%，未发现关联证据（OR，0.97[95%置信区间，0.91 - 1.03]），且无显著异质性（I² = 0）。此外，对1781例CHD病例的母亲（其中829例在本研究中进行了基因分型）和19861例对照进行的荟萃分析显示，母亲的C677T基因型与后代CHD风险之间没有关联证据（OR，1.13[95%置信区间，0.87 - 1.47]）。在不同膳食叶酸水平地区的大型研究中，MTHFR基因型与CHD风险之间没有显著关联。
直接影响血浆叶酸水平的MTHFR C677T多态性与CHD风险无关。发表偏倚似乎在很大程度上影响了关于这种基因关联的文献。
