Pharmacy Intravenous Admixture Services, Qilu Hospital, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, China.
BMC Med Genet. 2012 Sep 4;13:77. doi: 10.1186/1471-2350-13-77.
5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk.
Relevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity.
C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.
The present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.
5,10-亚甲基四氢叶酸还原酶（MTHFR）的 C677T 和 A1298C 变异与急性淋巴细胞白血病（ALL）风险降低有关。然而，来自单独的、效力不足的研究的结果存在冲突。我们对 MTHFR 多态性与 ALL 风险之间的关联进行了更新的荟萃分析。
通过 PUBMED 和 EMBASE 数据库搜索相关文献。通过比值比（ORs）评估 MTHFR C677T 和 A1298C 多态性与 ALL 风险之间的关系。评估了异质性和发表偏倚。进行了荟萃回归分析以评估潜在的异质性来源。
C677T 多态性与 ALL 风险降低相关（等位基因对比：ORRE = 0.91，95% CI：0.83-0.99）。亚组分析表明，MTHFR C677T 变异与儿童和白种人 ALL 的易感性降低有关。荟萃回归表明，随着病例组中性别比（M/F）的增加，T 等位基因与 ALL 之间关联的对数 OR 增加（P = 0.01）。关于 A1298C 多态性，未观察到显著相关性（等位基因对比：ORRE = 1.01，95% CI：0.91-1.11）。C677T 或 A1298C 多态性均无发表偏倚。
本荟萃分析表明，MTHFR 基因中的 C677T 多态性而非 A1298C 与 ALL 风险降低有关，特别是在儿童和白种人患者中。我们的研究结果表明，C677T 多态性对 ALL 易感性的影响受病例中性别比的影响（M/F）。由于叶酸摄入可能是一个潜在的混杂因素，因此在未来的前瞻性研究中包括这个因素是必要的。进一步的荟萃分析研究至少应按叶酸水平和性别分层，以提供更有力和有信息价值的结果。
