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叶酸代谢途径中的遗传变异与神经管缺陷风险：已发表文献的荟萃分析。

Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature.

机构信息

Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

PLoS One. 2013 Apr 4;8(4):e59570. doi: 10.1371/journal.pone.0059570. Print 2013.

DOI:10.1371/journal.pone.0059570
PMID:23593147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3617174/
Abstract

BACKGROUND

Neural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996-2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association.

METHODS AND FINDINGS

We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07-1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24-1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models.

CONCLUSIONS

Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.

摘要

背景

神经管缺陷（NTDs）是全球最常见和最严重的先天畸形之一。已有研究报道，叶酸代谢途径中关键基因的多态性与 NTDs 的发病风险相关。然而，这些已发表的研究结果存在争议。我们对文献（1996-2011 年）进行了调查，并进行了全面的荟萃分析，以提供该关联的经验证据。

方法和发现

我们研究了来自 47 个研究人群的 5 个遗传变异的影响，共涉及 85 个病例对照比较，MTHFR C677T（42 项研究；4374 例病例，7232 例对照），MTHFR A1298C（22 项研究；2602 例病例，4070 例对照），MTR A2756G（9 项研究；843 例病例，1006 例对照），MTRR A66G（8 项研究；703 例病例，1572 例对照），和 RFC-1 A80G（4 项研究；1107 例病例，1585 例对照）。我们发现 MTHFR C677T 的显性作用有令人信服的证据（OR 1.23；95%CI 1.07-1.42），RFC-1 A80G 的显性作用有提示性证据（OR 1.55；95%CI 1.24-1.92）。然而，我们没有发现 MTHFR A1298C、MTR A2756G、MTRR A66G 在 NTDs 的显性、隐性或等位基因模型中的风险有显著影响。

结论

我们的荟萃分析强烈提示变异型 MTHFR C677T 与 NTDs 风险增加显著相关，而 RFC-1 A80G 则有提示性关联。然而，其他涉及叶酸途径的变异在 NTDs 的易感性方面没有显示出任何显著的边缘关联的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/43bef3cb90d5/pone.0059570.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/a841f801d383/pone.0059570.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/3da9321eb6c0/pone.0059570.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/a5700844f70d/pone.0059570.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/875408d3e844/pone.0059570.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/8dd103582dd7/pone.0059570.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/43bef3cb90d5/pone.0059570.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/a841f801d383/pone.0059570.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/3da9321eb6c0/pone.0059570.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/a5700844f70d/pone.0059570.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/875408d3e844/pone.0059570.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/8dd103582dd7/pone.0059570.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f70/3617174/43bef3cb90d5/pone.0059570.g006.jpg

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