Fudan university, 130 Dong'an Road, Shanghai 200032, China.
Gene. 2013 Feb 10;514(2):105-11. doi: 10.1016/j.gene.2012.10.091. Epub 2012 Nov 29.
Recurrent pregnancy loss is an important clinical problem. Recently, high-level homocysteine in blood has been considered as a possible cause. Genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) have been proved to be the common hereditary factors of high-level homocysteine. The association between MTHFR polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported but with controversial results. The purpose of present study is to collect and analyze published available data, and evaluate the association between MTHFR polymorphisms and URPL.
A meta-analysis was performed to examine the association between MTHFR polymorphisms (C677T and A1298C) and URPL. Odds ratio (OR) and its 95% confidence interval (CI) were used in each study of genotype and allele contrast.
RESULT(S): MTHFR C677T: The analysis included 3559 URPL cases and 5097 healthy controls. Overall random-effects odds ratios (ORs) were 1.68 (95% CI, 1.32-2.13; P<0.0001) for TT versus total genotypes, 1.35 (95% CI, 1.04-1.76; P=0.0224) for TT and CT genotype combined versus total genotypes and 1.34 (95%CI, 1.13-1.58; P<0.0001) for T versus total alleles. Although significant heterogeneity was found in C677T, it became weaker in the East Asian subgroup and the mixed subgroup when separated by ethnic subgroups. The results showed significant association between MTHFR C677T and URPL in the East Asian subgroup (ORs 2.11 for TT versus total genotype (P=0.0004) and 1.53 for T versus total alleles (P<0.0001)) and in the mixed subgroup (ORs 3.47 for TT versus total genotypes (P<0.0001) and 1.80 for T versus total alleles (P<0.027)), but not in Caucasian subgroup. MTHFR A1298C: The study involved 1163 URPL cases and 1061 healthy controls. Overall random-effects odds ratios (ORs) were 1.37 (95% CI, 0.71-2.67; P=0.3456) for CC versus total genotypes, 1.16 (95%CI, 0.98-1.38; P=0.0833) for CC+AC versus total genotypes and 1.04 (95%CI, 0.84-1.29; P=0.7112) for C versus total alleles. No significant association between MTHFR A1298C polymorphism and URPL was found.
These results indicate a significant association between MTHFR C677T mutation and URPL in the East Asian subgroup and mixed subgroup, but no significance in MTHFR A1298C mutation.
复发性流产是一个重要的临床问题。最近，血液中高水平的同型半胱氨酸被认为是一个可能的原因。亚甲基四氢叶酸还原酶（MTHFR）的遗传多态性已被证明是高水平同型半胱氨酸的常见遗传因素。MTHFR 多态性与不明原因复发性流产（URPL）之间的关联已经有报道，但结果存在争议。本研究的目的是收集和分析已发表的可用数据，并评估 MTHFR 多态性与 URPL 之间的关系。
采用荟萃分析方法研究 MTHFR 多态性（C677T 和 A1298C）与 URPL 的关系。每个研究的基因型和等位基因对照均采用比值比（OR）及其 95%置信区间（CI）。
MTHFR C677T：分析纳入 3559 例 URPL 病例和 5097 例健康对照。总的随机效应 ORs 为 TT 与总基因型相比为 1.68（95%CI，1.32-2.13；P<0.0001），TT 和 CT 基因型与总基因型相比为 1.35（95%CI，1.04-1.76；P=0.0224），T 与总等位基因相比为 1.34（95%CI，1.13-1.58；P<0.0001）。虽然 C677T 存在显著异质性，但按亚组进行分层后，在东亚亚组和混合亚组中异质性减弱。结果显示，在东亚亚组（TT 与总基因型相比的 OR 为 2.11（P=0.0004），T 与总等位基因相比的 OR 为 1.53（P<0.0001））和混合亚组（TT 与总基因型相比的 OR 为 3.47（P<0.0001），T 与总等位基因相比的 OR 为 1.80（P<0.027））中，MTHFR C677T 与 URPL 之间存在显著关联，但在白种人亚组中无显著关联。MTHFR A1298C：该研究纳入 1163 例 URPL 病例和 1061 例健康对照。总的随机效应 ORs 为 CC 与总基因型相比为 1.37（95%CI，0.71-2.67；P=0.3456），CC+AC 与总基因型相比为 1.16（95%CI，0.98-1.38；P=0.0833），C 与总等位基因相比为 1.04（95%CI，0.84-1.29；P=0.7112）。MTHFR A1298C 多态性与 URPL 之间无显著关联。
这些结果表明，MTHFR C677T 突变与东亚亚组和混合亚组的 URPL 之间存在显著关联，但 MTHFR A1298C 突变无显著关联。
