Bagos Pantelis G, Karnaouri Anthi C, Nikolopoulos Georgios K, Hamodrakas Stavros J
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens, Greece.
Mult Scler. 2007 Mar;13(2):156-68. doi: 10.1177/1352458507078059.
We conducted a meta-analysis concerning the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms with the risk of developing multiple sclerosis (MS). We identified 18 eligible studies summarizing information about 3375 MS cases and 2930 healthy controls. Two polymorphisms were of interest: the exon 1 +49 A/G polymorphism (in 18 studies) and the promoter-318 C/T polymorphism (in 10 studies). Using random-effects methods we found no evidence for association of the various contrasts of genotypes (or allele frequencies) with the disease. There was significant between-studies heterogeneity that could not be explained by the ethnicity of the populations studied or by other summary measures (gender, disease course, latitude). The major finding of the meta-analysis, apart from the lack of an overall association, consists of detecting a significant time trend of the OR for the contrast of GA versus GG+AA genotypes of the exon 1 +49 A/G polymorphism. In particular, using cumulative meta-analysis we found that the large number of conflicting results on the subject was triggered by the early appearance of a highly significant published result (a study that indicated a significant association of the genotype with the disease).
我们进行了一项荟萃分析，以研究细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因多态性与多发性硬化症（MS）发病风险之间的关联。我们确定了18项符合条件的研究，这些研究总结了3375例MS病例和2930例健康对照的信息。有两个多态性值得关注：外显子1 +49 A/G多态性（18项研究）和启动子 -318 C/T多态性（10项研究）。使用随机效应方法，我们没有发现基因型（或等位基因频率）的各种对比与疾病之间存在关联的证据。研究间存在显著的异质性，无法用所研究人群的种族或其他汇总指标（性别、病程、纬度）来解释。除了缺乏总体关联外，荟萃分析的主要发现是检测到外显子1 +49 A/G多态性的GA与GG + AA基因型对比的OR存在显著的时间趋势。特别是，使用累积荟萃分析我们发现，该主题上大量相互矛盾的结果是由一个高度显著的已发表结果（一项表明该基因型与疾病存在显著关联的研究）的早期出现所引发的。
