MTRR基因A66G多态性与儿童急性淋巴细胞白血病关系的Meta分析

MTRR Gene A66G Polymorphism and Pediatric Acute Lymphoblastic Leukemia:A Meta-analysis

目的评估甲硫氨酸合成酶还原酶(MTRR)基因A66G多态性与儿童急性淋巴细胞白血病(ALL)发生风险的关系。方法全面检索Pub Med、Elsevier、Embase、中文期刊全文数据库(CNKI)和万方数据库,收集探索MTRR基因A66G多态性与儿童ALL发生关系的病例对照研究,纳入符合入选标准的文献并评估其质量。优势比(ORs)及95%可信区间(CIs)评估关联强度。应用Rev Man 5.2软件对纳入研究进行异质性检验和效应值合并,漏斗图评估发表性偏倚,敏感性分析采用逐一排除的方法以评估结果的稳定性。结果共纳入7篇文献,包括儿童ALL患者2 326例,对照3 090例。异质性检验结果表明纳入研究间无显著异质性,采用固定效应模型合并数据。Meta分析结果示,在整体人群纯合子模型和显性模型发现MTRR A66G多态性与儿童ALL风险有关联(GG vs.AA:OR=0.81,95%CI:0.69~0.95,P=0.009;AG+GG vs.AA:OR=0.87,95%CI:0.77~0.98,P=0.03);根据种族进行亚组分析时在白种人群中发现显著性关联(AG vs.AA:OR=0.84,95%CI:0.72~0.99,P=0.04;GG vs.AA:OR=0.79,95%CI:0.66~0.95,P=0.01;AG+GG vs.AA:OR=0.82,95%CI:0.71~0.96,P=0.01)。漏斗图未检测出显著性发表性偏倚,敏感性分析表明结果稳定可靠。结论目前Meta分析表明MTRR基因A66G多态性与儿童ALL发生风险存在关联,尤其在白种人群。

Objective To evaluate the relationship between methionine synthase reductase(MTRR) A66 G genetic polymorphism and the risk of pediatric acute lymphoblastic leukemia(ALL). Methods Relevant literatures were extensively searched in Pub Med, Elsevier, Embase, China National Knowledge Infrastructure and Wanfang Databases for collecting the case-control studies investigating the relationship between MTRR A66 G genetic polymorphism and pediatric ALL. Odds ratios(ORs) with 95% confidence intervals(CIs) were applied to assess the strength of association. The Rev Man 5.2 software was applied for heterogeneity test and combined ORs and their 95%CIs calculation. Publication bias was assessed through funnel plot and sensitivity analysis was performed by sequential remove individual studies to assess the stability of the results. Results Seven studies bearing 2,326 cases and 3,090 controls met the inclusion criteria and were included in the Meta-analysis. There was no significant heterogeneity among the included studies and fixed-effects model was applied to combine the data. The results suggested that there was significant association between MTRR A66 G polymorphism and pediatric ALL risk in overall comparisons under homozygote and dominant genetic models(GG vs. AA: OR=0.81, 95%CI: 0.69-0.95, P=0.009; AG+GG vs. AA: OR=0.87, 95%CI: 0.77-0.98, P=0.03). In the subgroup analysis by ethnicity, significant association was found in Caucasians(AG vs. AA: OR=0.84, 95%CI: 0.72-0.99, P=0.04; GG vs. AA: OR=0.79, 95%CI: 0.66-0.95, P=0.01; AG+GG vs. AA: OR=0.82, 95%CI: 0.71-0.96, P=0.01). No significant publication bias was detected by funnel plot and sensitivity analysis suggested the robustness of the results. Conclusion The present Meta-analysis suggests that MTRR A66 G polymorphism is associated with pediatric ALL risk, especially in Caucasian populations.