Infants' MTHFR Polymorphisms and Nonsyndromic Orofacial Clefts Susceptibility: A Meta-Analysis Based on 17 Case-Control Studies
Infants' MTHFR Polymorphisms and Nonsyndromic Orofacial Clefts Susceptibility: A Meta-Analysis Based on 17 Case-Control Studies
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DOI：
10.1002/ajmg.a.35503
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发表时间：
2012-09-01
影响因子：
2
通讯作者：
Wang, Lin
中科院分区：
文献类型：
--
作者：
Pan, Yongchu;Zhang, Weibing;Wang, Lin
亚甲基四氢叶酸还原酶（MTHFR）是叶酸代谢的重要酶，被认为参与了非综合征性口面裂（NSOC）的发生。然而，当评估婴儿MTHFR C677 T和A1298 C多态性与NSOC风险之间的关联时，已经取得了相互矛盾的结果。为了获得更精确的估计，这些协会，荟萃分析招募17例病例对照研究进行。在亚洲人中，我们发现，与CC野生型纯合子相比，婴儿MTHFR C677 T变异的CT杂合子、TT纯合子和CT/TT可能导致NSOC风险升高（CT与CC的OR = 1.741，95%CI = 1.043-2.907; TT与CC的OR = 2.311，95%CI = 1.313-4.041; CT/TT与CC的OR = 1.740，95%CI = 1.051-2.882）。在亚洲人群中，MTHFR 677 T等位基因与C等位基因相比也有类似的效应（OR = 1.420，95% CI = 1.191-1.693）。按疾病类型分层分析，在隐性遗传模型下，CT/CC可降低CL/P的易感性（OR = 0.854，95% CI = 0.730-1.000）。MTHFR A1298 C等位基因在白种人病例组显著低于对照组（OR = 0.711，95% CI = 0.641-0.790），提示MTHFR A1298 C等位基因对白种人NSOC具有保护作用。结论：MTHFR基因C677 T和A1298 C多态性与NSOC的发生有关。(C)2012 Wiley Periodicals，Inc.
Methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, is thought to be involved in the development of nonsyndromic orofacial clefts (NSOC). However, conflicting results have been achieved when evaluating the associations between infants' MTHFR C677T and A1298C polymorphisms and the risk of NSOC. To obtain more precise estimations of these associations, a meta-analysis recruiting 17 case-control studies was performed. Among Asians we found that CT heterozygote, TT homozygote, and CT/TT of infants' MTHFR C677T variant could contribute to elevated risks of NSOC, compared with CC wild-type homozygote (OR = 1.741, 95% CI = 1.043-2.907 for CT vs. CC, OR = 2.311, 95% CI = 1.313-4.041 for TT vs. CC, and OR = 1.740, 95% CI = 1.051-2.882 for CT/TT vs. CC, respectively). Similar effect was also observed on MTHFR 677T T allele, when using C allele as a reference in Asians (OR = 1.420, 95% CI = 1.191-1.693, for T allele vs. C allele). Furthermore, in stratified analysis by types of disease, CT/CC was suggested to confer decreased susceptibility to CL/P under recessive genetic model (OR = 0.854, 95% CI = 0.730-1.000). For MTHFR A1298C, the MTHFR 1298C allele in the case group of Caucasians was significantly lower than that in the control group, suggesting a protective effect against NSOC in Caucasian populations (OR = 0.711, 95% CI = 0.641-0.790, for C allele vs. A allele). In conclusion, the meta-analysis provided confirmative evidences that infants' MTHFR C677T and A1298C polymorphisms were involved in the development of NSOC. (C) 2012 Wiley Periodicals, Inc.