Zintzaras Elias, Koufakis Theocharis, Ziakas Panayiotis D, Rodopoulou Paraskevi, Giannouli Stavroula, Voulgarelis Michael
Evidence-Based Medicine Unit, Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
Eur J Epidemiol. 2006;21(7):501-10. doi: 10.1007/s10654-006-9027-8. Epub 2006 Aug 9.
A meta-analysis of case-control studies that investigated the association between the C677T and/or A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and acute lymphoblastic leukemia (ALL) was carried out. Pooled odds ratios (OR) of various genetic contrasts of each polymorphism were estimated using random (RE) and fixed effects (FE) models. Pooled ORs for combined genotypes and haplotypes were estimated after adjustment for study effect using a log-linear model and the expectation-maximization algorithm in combination with log-linear modeling, respectively. The recessive model for allele 1298C produced a rather marginal association: RE OR: 0.67; 95% confidence interval (CI): 0.46-0.99 and FE OR: 0.64; 95% CI: 0.49-0.84. In Caucasians, the results of the recessive model for allele 1298C was consisted with a protective effect of ALL development: FE OR: 0.63; 95% CI: 0.46-0.87. In childhood ALL, according to the results of the allele contrast and the recessive model for 677T allele it was conceivable that a protective effect exist: RE OR = 0.74; 95% CI: 0.57-0.96 and RE OR: 0.69; 95% CI: 0.51-0.94, respectively. The combined genotypes produced significant pooled OR for the 677CC/1298CC relative to 677CC/1298AA (OR: 0.54; 95% CI: 0.36-0.80). The haplotype 677C/1298C might be more protective to ALL relative to haplotype 677C/1298A (OR: 0.77; 95% CI: 0.61-0.97). When studies not in Hardy-Weinberg equilibrium (HWE) were corrected to account for departures from HWE, then, the pattern of results remained the same. Overall, there is high heterogeneity between the studies in both polymorphisms. A differential magnitude of effect in large versus small studies and alteration of early extremes effects existed.
开展了一项病例对照研究的荟萃分析，该研究调查了亚甲基四氢叶酸还原酶（MTHFR）基因中的C677T和/或A1298C多态性与急性淋巴细胞白血病（ALL）之间的关联。使用随机效应（RE）模型和固定效应（FE）模型估计了每种多态性各种遗传对比的合并比值比（OR）。分别使用对数线性模型和期望最大化算法结合对数线性建模，在对研究效应进行校正后，估计了合并基因型和单倍型的合并OR。等位基因1298C的隐性模型产生了一种相当微弱的关联：随机效应模型OR为0.67；95%置信区间（CI）：0.46 - 0.99，固定效应模型OR为0.64；95%CI：0.49 - 0.84。在白种人中，等位基因1298C隐性模型的结果表明其对ALL的发生有保护作用：固定效应模型OR为0.63；95%CI：0.46 - 0.87。在儿童ALL中，根据等位基因对比结果以及677T等位基因的隐性模型，可以推测存在保护作用：随机效应模型OR = 0.74；95%CI：0.57 - 0.96以及随机效应模型OR为0.69；95%CI：0.51 - 0.94。相对于677CC/1298AA，合并基因型677CC/1298CC产生了显著的合并OR（OR：0.54；95%CI：0.36 - 0.80）。相对于单倍型677C/1298A，单倍型677C/1298C可能对ALL更具保护作用（OR：0.77；95%CI：0.61 - 0.97）。当对不符合哈迪 - 温伯格平衡（HWE）的研究进行校正以考虑偏离HWE的情况时，结果模式保持不变。总体而言，这两种多态性的研究之间存在高度异质性。大型研究与小型研究中效应大小存在差异，且早期极端效应存在改变。
