Immunology Department, Hospital Clínico San Carlos, Madrid, Spain.
Eur J Hum Genet. 2010 Jul;18(7):794-9. doi: 10.1038/ejhg.2010.15. Epub 2010 Feb 24.
Interleukin (IL)-2/IL-2R signalling promotes proliferation and survival of activated T cells and has an essential non-redundant role in the production of regulatory T cells. Associations with different autoimmune diseases of polymorphisms in a linkage disequilibrium block in which the IL2/IL21 genes map (4q27), and also in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these three genes were studied in 430 multiple sclerosis (MS) patients and in 550 ethnically matched controls from Madrid (Spain). Replication and meta-analysis with results from an independent cohort of 771 MS patients and 759 controls from Andalucía (Spain) confirmed the association of polymorphisms in the IL2RA gene (P(Mantel-Haenszel,) odds ratio (OR)(M-H) (95% confidence interval, CI) for rs2104286: 0.0001, 0.75 (0.65-0.87); for rs11594656/rs35285258: 0.004, 1.19 (1.06-1.34); for rs41295061: 0.03, 0.77 (0.60-0.98)); showed a trend for association of the IL2/IL21 rs6822844 (P(M-H)=0.07, OR(M-H) (95% CI)=0.86 (0.73-1.01)), but did not corroborate the association for IL2RB. Regression analyses of the combined Spanish cohort revealed the independence of two IL2RA association signals: rs2104286 and rs11594656/rs35285258. The relevant role of the IL2RA gene on MS susceptibility adds support to its common effect on autoimmune risk and the suggestive association of IL2/IL21 warrants further investigation.
白细胞介素（IL）-2/IL-2R 信号促进活化 T 细胞的增殖和存活，并在调节性 T 细胞的产生中具有不可或缺的非冗余作用。通过全基因组研究，在 IL2/IL21 基因所在的连锁不平衡块（4q27）中以及编码 IL2RA 和 IL2RB 亚基的基因（分别位于 10p15 和 22q13）中，发现了与不同自身免疫性疾病相关的多态性。在来自马德里（西班牙）的 430 名多发性硬化症（MS）患者和 550 名种族匹配的对照中研究了这三个基因的多态性。与来自安达卢西亚（西班牙）的 771 名 MS 患者和 759 名对照的独立队列的复制和荟萃分析证实了 IL2RA 基因多态性的关联（rs2104286：Mantel-Haenszel 检验 P 值（OR）（M-H）（95%置信区间，CI）：0.0001，0.75（0.65-0.87）；rs11594656/rs35285258：0.004，1.19（1.06-1.34）；rs41295061：0.03，0.77（0.60-0.98））；rs6822844 与 IL2/IL21 呈关联趋势（Mantel-Haenszel 检验 P 值（OR）（M-H）（95%置信区间，CI）：0.07，0.86（0.73-1.01）），但未证实 IL2RB 的相关性。对西班牙联合队列的回归分析揭示了两个 IL2RA 关联信号的独立性：rs2104286 和 rs11594656/rs35285258。IL2RA 基因在 MS 易感性上的重要作用进一步支持了其对自身免疫风险的共同作用，而对 IL2/IL21 的提示性关联则需要进一步研究。
