Márquez Ana, Varadé Jezabel, Robledo Gema, Martínez Alfonso, Mendoza Juan Luis, Taxonera Carlos, Fernández-Arquero Miguel, Díaz-Rubio Manuel, Gómez-García María, López-Nevot Miguel Angel, de la Concha Emilio G, Martín Javier, Urcelay Elena
Department of Immunology, Hospital Clínico San Carlos, Madrid, Spain.
Eur J Hum Genet. 2009 Oct;17(10):1304-8. doi: 10.1038/ejhg.2009.50. Epub 2009 Apr 1.
Independent genome-wide association studies highlighted the function of CLEC16A/KIAA0350 polymorphisms modifying the risk to either multiple sclerosis (rs6498169) or type 1 diabetes (rs2903692). This C-type lectin gene maps to a linkage disequilibrium block at 16p13 and a functional role of this gene could be envisaged for other immune-related conditions, such as inflammatory bowel disease (IBD). The present study, aimed at investigating the association of those two polymorphisms with IBD, included 720 IBD patients and 550 ethnically matched healthy controls. The effect of rs2903692 previously described in diabetes was observed specifically for Crohn's disease (CD) patients lacking the main susceptibility factor described to date, that is, three polymorphisms within another pattern recognition gene, NOD2/CARD15 (NOD2(-) vs NOD2(+) CD patients, G vs A: P=0.008; OR (95% CI)=1.54 (1.10-2.15); NOD2(-) CD patients vs controls: P=0.008; OR (95% CI)=1.37 (1.08-1.73)). Replication of these findings was performed in independent Spanish cohorts of 544 IBD patients and 340 controls and the combined data yielded significant differences (405 NOD2(-) vs 204 NOD2(+) CD patients, G vs A: P=0.0012; OR(M-H) (95% CI)=1.49 (1.17-1.90); NOD2(-) CD patients vs controls: P=0.0007; OR(M-H) (95% CI)=1.35 (1.13-1.60)). The pooled analysis of the ulcerative colitis patients vs controls also yielded a significant risk (P=0.0005; OR (95% CI)=1.52 (1.19-1.93)). These data would suggest that microbial recognition through different pathways seems to converge in the development of these polygenic bowel diseases.
独立的全基因组关联研究突出了CLEC16A/KIAA0350基因多态性在改变多发性硬化症（rs6498169）或1型糖尿病（rs2903692）风险方面的作用。这个C型凝集素基因定位于16p13的一个连锁不平衡区域，并且可以设想该基因在其他免疫相关疾病，如炎症性肠病（IBD）中具有功能作用。本研究旨在调查这两种多态性与IBD的关联，纳入了720例IBD患者和550例种族匹配的健康对照。先前在糖尿病中描述的rs2903692的作用，在缺乏迄今为止所描述的主要易感因素，即另一个模式识别基因NOD2/CARD15内的三个多态性的克罗恩病（CD）患者中特别观察到（NOD2（-）与NOD2（+）的CD患者，G与A：P = 0.008；比值比（95%可信区间）= 1.54（1.10 - 2.15）；NOD2（-）的CD患者与对照：P = 0.008；比值比（95%可信区间）= 1.37（1.08 - 1.73））。在544例IBD患者和340例对照的独立西班牙队列中对这些发现进行了重复验证，合并数据产生了显著差异（405例NOD2（-）与204例NOD2（+）的CD患者，G与A：P = 0.0012；比值比（M-H）（95%可信区间）= 1.49（1.17 - 1.90）；NOD2（-）的CD患者与对照：P = 0.0007；比值比（M-H）（95%可信区间）= 1.35（1.13 - 1.60））。溃疡性结肠炎患者与对照的汇总分析也产生了显著风险（P = 0.0005；比值比（95%可信区间）= 1.52（1.19 - 1.93））。这些数据表明，通过不同途径的微生物识别似乎在这些多基因肠道疾病的发生发展中汇聚。
