Immunology Department, Medicine School and Habib Bourguiba Hospital, Sfax, Tunisia.
Hum Immunol. 2011 Dec;72(12):1204-9. doi: 10.1016/j.humimm.2011.10.002. Epub 2011 Oct 8.
The identification of susceptibility genes for inflammatory bowel disease (IBD) is key to understanding pathogenic mechanisms. Recently, the results of genetic association studies have highlighted many loci that are shared among several autoimmune diseases. We aimed to study the genetic epidemiology of polymorphisms in specific genes previously associated with other autoimmune diseases, namely the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes. Twelve polymorphisms in the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes were genotyped in a cohort of 107 IBD patients (39 Crohn's disease [CD] and 68 ulcerative colitis [UC]) and 162 controls from southern Tunisia. One CREM single nucleotide polymorphism (SNP) displayed evidence for genetic association with IBD (p=8.7×10(-4), odds ratio [OR]=2.84 [1.58; 5.09]). One STAT4 SNP (p=0.026; OR=1.65 [1.06; 2.58]) exhibited a marginal association with UC but not with CD. No significant association was observed with the SNPs in STAT5a, IRF5, and STAT5b. These results suggest that common variants of the CREM gene are involved in the genetic component conferring general susceptibility to IBD, whereas STAT4 appears to be more specifically associated with UC. This work provides motivation for studies aiming to replicate these findings in larger populations.
炎症性肠病(IBD)易感性基因的鉴定是理解发病机制的关键。最近,遗传关联研究的结果突出了许多在几种自身免疫性疾病中共享的基因位点。我们旨在研究先前与其他自身免疫性疾病相关的特定基因中多态性的遗传流行病学,即 CREM、STAT4、STAT5a、Stat5b 和 IRF5 基因。在来自突尼斯南部的 107 名 IBD 患者(39 名克罗恩病[CD]和 68 名溃疡性结肠炎[UC])和 162 名对照中,对 CREM、STAT4、STAT5a、Stat5b 和 IRF5 基因中的 12 个多态性进行了基因分型。一个 CREM 单核苷酸多态性(SNP)显示与 IBD 存在遗传关联的证据(p=8.7×10(-4),优势比[OR]=2.84 [1.58; 5.09])。一个 STAT4 SNP(p=0.026;OR=1.65 [1.06; 2.58])与 UC 存在边缘关联,但与 CD 无关。STAT5a、IRF5 和 STAT5b 中的 SNP 没有观察到显著关联。这些结果表明,CREM 基因的常见变体参与了赋予 IBD 一般易感性的遗传成分,而 STAT4 似乎与 UC 更密切相关。这项工作为旨在在更大人群中复制这些发现的研究提供了动力。