Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, P.R. China.
J Endocrinol Invest. 2010 Nov;33(10):751-5. doi: 10.1007/BF03346682. Epub 2010 Mar 22.
Graves' disease (GD) is a common autoimmune disorder with genetic predisposition. There is strong evidence that the Chr.5q31-33 region, which contains the immune response cytokine genes [interleukin (IL)-3, IL-4, IL-5, IL-9, and IL-13], is linked to autoimmune thyroid disorders in Chinese and Japanese populations. The aim of the present study is to elucidate whether the single nucleotide polymorphisms (SNP) and the interaction of variants in the 5 genes are associated with the development of GD and Graves' ophthalmopathy (GO).
GD patients (no.=751), with 190 of GO patients and healthy control subjects (no.=748) were included in this study. Six SNP [rs40401 (IL-3), rs2070874 (IL-4), rs2069812 (IL-5), rs1859430 (IL-9), rs2069868 (IL-9), and rs20541 (IL-13)] were genotyped by SNPstream Genotyping System.
There was a significant increase of C allele of rs40401 in GD [odds ratio (OR)=1.18 [95% confidence interval (CI): 1.02-1.36], pallele=0.028] and GO [OR=1.30 (95%CI: 1.04-1.63), pallele=0.022] patients compared with those in the controls. The C allele of the rs2069812 was also significantly associated with GD [OR=1.22 (95%CI: 1.04-1.44), pallele=0.015] and GO [OR=1.45 (95%CI: 1.13-1.86), pallele=0.003] patients. Haplotype analysis showed a predominant increase of the 2 SNP (rs40401-rs2069812, CC) and all the 6 SNP (CCCCCC) haplotype in GD (OR=1.70, OR=3.70, respectively) and even stronger in GO (OR=2.18, OR=7.01, respectively) patients.
The results suggested that the polymorphism of IL-3 (rs40401) and IL-5 (rs2069812) were associated with GD and GO susceptibility in Chinese population. The interaction of 6-locus from the 5 genes might confer higher risk for GD and GO than single risk allele.
Graves 病（GD）是一种常见的自身免疫性疾病，具有遗传易感性。有强有力的证据表明，包含免疫反应细胞因子基因[白细胞介素（IL）-3、IL-4、IL-5、IL-9 和 IL-13]的 Chr.5q31-33 区域与中国和日本人群的自身免疫性甲状腺疾病有关。本研究旨在阐明 5 个基因中的单核苷酸多态性（SNP）及其变体的相互作用是否与 GD 和 Graves 眼病（GO）的发生有关。
本研究纳入了 751 例 GD 患者、190 例 GO 患者和 748 例健康对照者。采用 SNPstream 基因分型系统对 6 个 SNP[rs40401（IL-3）、rs2070874（IL-4）、rs2069812（IL-5）、rs1859430（IL-9）、rs2069868（IL-9）和 rs20541（IL-13）]进行基因分型。
与对照组相比，GD [比值比（OR）=1.18（95%置信区间（CI）：1.02-1.36），等位基因=0.028]和 GO [OR=1.30（95%CI：1.04-1.63），等位基因=0.022]患者的 rs40401 中 C 等位基因显著增加。rs2069812 的 C 等位基因也与 GD [OR=1.22（95%CI：1.04-1.44），等位基因=0.015]和 GO [OR=1.45（95%CI：1.13-1.86），等位基因=0.003]患者显著相关。单体型分析显示，GD 患者 rs40401-rs2069812 （CC）和 6 个 SNP（CCCCCC）单体型的出现频率明显增加（OR=1.70，OR=3.70），GO 患者的增加更为明显（OR=2.18，OR=7.01）。
研究结果提示，IL-3（rs40401）和 IL-5（rs2069812）的多态性与中国人群的 GD 和 GO 易感性有关。5 个基因的 6 个基因座的相互作用可能比单个风险等位基因赋予更高的 GD 和 GO 风险。
