Wang Haigang, Meng Lujing, Zhao Lixia, Wang Jiali, Liu Xinchun, Mi Wenjie
Department of Pharmacy, Qilu Hospital, Shandong University, Jinan, China.
Genet Test Mol Biomarkers. 2012 Dec;16(12):1401-7. doi: 10.1089/gtmb.2012.0184. Epub 2012 Oct 12.
Two polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, were hypothesized to decrease the risk of acute lymphoblastic leukemia (ALL). Studies examining the associations between these two polymorphisms and ALL susceptibility drew inconsistent results. To obtain a reliable conclusion in a Chinese population, we carried out a meta-analysis. In total, 11 studies on C677T polymorphism (1597 cases and 2295 controls) and 10 studies on A1298C polymorphism (1553 cases and 2224 controls) were included in the meta-analysis. We found a significant association between the 677T variant and reduced ALL risk in Chinese children (Dominant model: odds ratio [OR(FE)]=0.73, 95% confidence interval [CI]: 0.63-0.86, p<0.01). Heterogeneity between the studies in the children subgroup was weak and vanished after excluding one study deviating from HWE in the control group (p>0.1). In the adult subgroup, there was no significant association between the C677T variant and ALL risk (Dominant model: OR(RE)=0.88, 95% CI: 0.45-1.72, p=0.72). Significant heterogeneity was found in the adult subgroup in all the genetic model tests (p<0.1). The A1298C polymorphism had an effect on ALL risk neither in adults (Dominant model: OR(FE)=0.95, 95% CI: 0.71-1.27, p=0.72) nor in children (Dominant model: OR(FE)=1.02, 95% CI: 0.87-1.21, p=0.77). No significant heterogeneity between studies on A1298C polymorphism was found in the meta-analysis (p>0.1). The results showed that there was a protective effect of the MTHFR C677T variant on ALL risk in Chinese children.
亚甲基四氢叶酸还原酶（MTHFR）基因中的两种多态性，即C677T和A1298C，被认为可降低急性淋巴细胞白血病（ALL）的风险。研究这两种多态性与ALL易感性之间关联的结果并不一致。为了在中国人群中得出可靠结论，我们进行了一项荟萃分析。该荟萃分析总共纳入了11项关于C677T多态性的研究（1597例病例和2295例对照）以及10项关于A1298C多态性的研究（1553例病例和2224例对照）。我们发现677T变异与中国儿童ALL风险降低之间存在显著关联（显性模型：比值比[OR(FE)] = 0.73，95%置信区间[CI]：0.63 - 0.86，p < 0.01）。儿童亚组研究之间的异质性较弱，在排除一项对照组偏离哈迪 - 温伯格平衡（HWE）的研究后异质性消失（p > 0.1）。在成人亚组中，C677T变异与ALL风险之间无显著关联（显性模型：OR(RE) = 0.88，95% CI：0.45 - 1.72，p = 0.72）。在所有遗传模型检验中，成人亚组均发现显著异质性（p < 0.1）。A1298C多态性在成人（显性模型：OR(FE) = 0.95，95% CI：0.71 - 1.27，p = 0.72）和儿童（显性模型：OR(FE) = 1.02，95% CI：0.87 - 1.21，p = 0.77）中对ALL风险均无影响。荟萃分析中未发现A1298C多态性研究之间存在显著异质性（p > 0.1）。结果表明，MTHFR C677T变异对中国儿童ALL风险具有保护作用。
