Büning Carsten, Geerdts Lars, Fiedler Thomas, Gentz Enno, Pitre Ghyslaine, Reuter Wolf, Luck Werner, Buhner Sabine, Molnar Tomas, Nagy Ferenc, Lonovics Janos, Dignass Axel, Landt Olfert, Nickel Renate, Genschel Janine, Lochs Herbert, Schmidt Hartmut H-J, Witt Heiko
Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany.
Am J Gastroenterol. 2006 Apr;101(4):786-92. doi: 10.1111/j.1572-0241.2006.00431.x. Epub 2006 Feb 22.
Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD).
Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test.
Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability.
We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD.
近期有报道称，盘状球蛋白5（DLG5）基因变异与炎症性肠病（IBD）相关。本研究旨在检测来自两个欧洲人群的668例IBD患者中6个DLG5变异的等位基因及单倍型关联。此外，我们评估了DLG5变异是否会改变克罗恩病（CD）患者的胃肠道通透性。
在两个研究人群中对6个DLG5变异（p.R30Q、p.P1371Q、p.G1066G、rs2289308、DLG_e26、p.D1507D）进行基因分型：（1）德国IBD患者（CD患者250例；溃疡性结肠炎（UC）患者150例）及德国健康对照者（422例）；（2）匈牙利IBD患者（CD患者144例；UC患者124例）及匈牙利健康对照者（205例）。针对CARD15突变和临床特征进行亚型分析。我们还通过三糖试验检测德国CD患者DLG5基因型在胃十二指肠和肠道通透性方面的差异。
在任一研究人群中，IBD患者与对照者之间DLG5变异的等位基因及基因型频率均无差异。实际上，p.R30Q多态性在对照者中的出现频率高于患者。CARD15突变的德国和匈牙利CD患者中DLG5基因型的分布与未发生CARD15突变的患者并无差异。我们也未观察到DLG5变异与临床参数之间存在任何关联。重要的是，DLG5变异与胃十二指肠或肠道通透性无关。
我们无法在德国或匈牙利人群中重现DLG5是IBD相关疾病易感基因这一结论。此外，我们没有证据表明DLG5变异参与了CD患者胃肠道通透性的改变。
