Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
Eur J Hum Genet. 2010 Jul;18(7):827-31. doi: 10.1038/ejhg.2009.240. Epub 2010 Jan 20.
A recent genome-wide association study conducted by the International Multiple Sclerosis Genetic Consortium (IMSGC) identified, among others, a number of putative multiple sclerosis (MS) susceptibility variants at position 1p22. Twenty-one SNPs positively associated with MS were located at the GFI-EVI5-RPL5-FAM69A locus. In this study, we performed an analysis and fine mapping of this locus, genotyping eight Tag-SNPs in 732 MS patients and 974 controls from Spain. We observed an association with MS in three of eight Tag-SNPs: rs11804321 (P=0.008, OR=1.29; 95% CI=1.08-1.54), rs11808092 (P=0.048, OR=1.19; 95% CI=1.03-1.39) and rs6680578 (P=0.0082, OR=1.23; 95% CI=1.07-1.41). After correcting for multiple comparisons and using logistic regression analysis to test the addition of each SNP to the most associated SNPs, we observed that rs11804321 alone was sufficient to model the association. This Tag-SNP captures two SNPs in complete linkage disequilibrium (r(2)=1), both located within the 17th intron of the EVI5 gene. Our findings agree with the corresponding data of the recent IMSGC study and present new genetic evidence that points to EVI5 as a factor of susceptibility to MS.
最近由国际多发性硬化症遗传联盟（IMSGC）进行的全基因组关联研究确定了 1p22 位置的多个多发性硬化症（MS）易感性变异。21 个与 MS 呈正相关的 SNP 位于 GFI-EVI5-RPL5-FAM69A 基因座。在这项研究中，我们对该基因座进行了分析和精细定位，对来自西班牙的 732 名 MS 患者和 974 名对照者进行了 8 个 Tag-SNP 的基因分型。我们观察到在 8 个 Tag-SNPs 中有 3 个与 MS 相关：rs11804321（P=0.008，OR=1.29；95%CI=1.08-1.54）、rs11808092（P=0.048，OR=1.19；95%CI=1.03-1.39）和 rs6680578（P=0.0082，OR=1.23；95%CI=1.07-1.41）。在进行多重比较校正并使用逻辑回归分析来测试每个 SNP 对最相关 SNP 的附加作用后，我们观察到仅 rs11804321 就足以模拟相关性。该 Tag-SNP 捕获了两个完全连锁不平衡（r(2)=1）的 SNP，均位于 EVI5 基因的第 17 个内含子内。我们的发现与最近 IMSGC 研究的相应数据一致，并提供了新的遗传证据，表明 EVI5 是 MS 易感性的一个因素。
