Török H-P, Glas J, Tonenchi L, Lohse P, Müller-Myhsok B, Limbersky O, Neugebauer C, Schnitzler F, Seiderer J, Tillack C, Brand S, Brünnler G, Jagiello P, Epplen J T, Griga T, Klein W, Schiemann U, Folwaczny M, Ochsenkühn T, Folwaczny C
Chirurgische Klinik und Poliklinik-Standort Innenstadt, and Medizinische Poliklinik-Standort Innenstadt, Ludwig-Maximilians-Universität München, Germany.
Gut. 2005 Oct;54(10):1421-7. doi: 10.1136/gut.2005.066340. Epub 2005 Jun 14.
Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions.
The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD15/NOD2 mutations was analysed.
No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non-fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery.
Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.
近期数据表明，位于先前描述的连锁区域中的盘状蛋白结构域蛋白5（DLG5）基因和有机阳离子转运体（OCTN）簇中存在炎症性肠病的因果基因变异。
对625例克罗恩病（CD）患者、363例溃疡性结肠炎（UC）患者和1012例健康对照者进行DLG5（113G→A、4136C→A和DLG5_e26）、溶质载体家族22成员4（SLC22A4，1672C→T）和溶质载体家族22成员5（SLC22A5，-207G→C）多态性评估。分析这些多态性与疾病易感性、临床表型以及与疾病相关的半胱天冬酶激活招募结构域蛋白15（CARD15）/核苷酸结合寡聚化结构域蛋白2（NOD2）突变的可能基因相互作用。
未观察到DLG5多态性与CD或UC有显著关联。OCTN-TC单倍型纯合子与CD风险增加相关（比值比[OR]=1.65）；在存在CARD15突变的情况下，这种相关性更强。基因型-表型分析显示，这种关联在结肠疾病患者中尤为明显。TC单倍型与非瘘管非纤维狭窄性疾病相关，疾病发病年龄较早，手术需求减少。
我们的观察结果表明DLG5多态性在炎症性肠病易感性中不起作用；而OCTN多态性与CD相关。然而鉴于本文观察到的关联较弱，在就这些变异在CD中的致病作用得出明确结论之前，对这些变异与炎症性肠病5（IBD5）单倍型标签单核苷酸多态性进行扩展连锁不平衡分析可能是可取的。
