Department of Medicine II-Grosshadern, University of Munich, Munich, Germany.
PLoS One. 2010 Apr 29;5(4):e10373. doi: 10.1371/journal.pone.0010373.
Recent studies demonstrated an association of STAT4 variants with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), indicating that multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 variants on the susceptibility and phenotype of inflammatory bowel diseases (IBD) in a large patient and control cohort.
METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 2704 individuals of Caucasian origin including 857 patients with Crohn's disease (CD), 464 patients with ulcerative colitis (UC), and 1383 healthy, unrelated controls was analyzed for seven SNPs in the STAT4 gene (rs11889341, rs7574865, rs7568275, rs8179673, rs10181656, rs7582694, rs10174238). In addition, a detailed genotype-phenotype analysis was performed. Our analysis revealed an association of the STAT4 SNP rs7574865 with overall decreased susceptibility to CD (p = 0.047, OR 0.86 [95% CI 0.74-0.99]). However, compared to CD patients carrying the wild type genotype, the STAT4 SNP rs7574865 was significantly associated with early CD onset (p = 0.021) and colonic CD (p = 0.008; OR = 4.60, 95% CI 1.63-12.96). For two other STAT4 variants, there was a trend towards protection against CD susceptibility (rs7568275, p = 0.058, OR 0.86 [95% CI 0.74-1.00]; rs10174238, p = 0.057, OR 0.86 [95% CI 0.75-1.00]). In contrast, we did not observe any association with UC susceptibility. Evidence for weak gene-gene interaction of STAT4 with the IL23R SNP rs11209026 was lost after Bonferroni correction.
CONCLUSIONS/SIGNIFICANCE: Our results identified the STAT4 SNP rs7574865 as a disease-modifying gene variant in colonic CD. However, in contrast to SLE and RA, the effect of rs7574865 on CD susceptibility is only weak.
最近的研究表明 STAT4 变体与系统性红斑狼疮 (SLE) 和类风湿性关节炎 (RA) 有关，这表明多种自身免疫性疾病共享共同的易感基因。因此，我们在一个大型的患者和对照队列中研究了 STAT4 变体对炎症性肠病 (IBD) 的易感性和表型的影响。
方法/主要发现：对来自 2704 名白种人个体的基因组 DNA 进行了分析，其中包括 857 名克罗恩病 (CD) 患者、464 名溃疡性结肠炎 (UC) 患者和 1383 名健康、无关的对照者，分析了 STAT4 基因中的 7 个 SNP(rs11889341、rs7574865、rs7568275、rs8179673、rs10181656、rs7582694、rs10174238)。此外，还进行了详细的基因型-表型分析。我们的分析表明，STAT4 SNP rs7574865 与 CD 的整体易感性降低有关（p = 0.047，OR 0.86 [95% CI 0.74-0.99]）。然而，与携带野生型基因型的 CD 患者相比，STAT4 SNP rs7574865 与 CD 的早期发病（p = 0.021）和结肠 CD（p = 0.008；OR = 4.60，95% CI 1.63-12.96）显著相关。对于另外两个 STAT4 变体，它们对 CD 的易感性有保护作用的趋势(rs7568275，p = 0.058，OR 0.86 [95% CI 0.74-1.00]；rs10174238，p = 0.057，OR 0.86 [95% CI 0.75-1.00])。相反，我们没有观察到与 UC 易感性有关的任何关联。经过 Bonferroni 校正后，STAT4 与 IL23R SNP rs11209026 之间的微弱基因-基因相互作用的证据丢失了。
结论/意义：我们的研究结果确定了 STAT4 SNP rs7574865 是结肠 CD 的一种疾病修饰基因变异。然而，与 SLE 和 RA 不同，rs7574865 对 CD 易感性的影响是微弱的。
