Department of Medical Genetics, University of Pécs, Pécs 7624, Hungary.
World J Gastroenterol. 2010 Jan 14;16(2):176-83. doi: 10.3748/wjg.v16.i2.176.
To investigate the interaction of interleukin-23 receptor (IL23R) (rs1004819 and rs2201841), autophagy-related 16-like 1 (ATG16L1) (rs2241880), caspase recruitment domain-containing protein 15 (CARD15) genes, and IBD5 locus in Crohn's disease (CD) patients.
A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped. Interactions and specific genotype combinations of a total of eight variants were tested. The variants of IBD5 locus (IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868), CARD15 (R702W rs2066845 and L1007fs rs2066847), ATG16L1 (rs2241880) and IL23R (rs1004819, rs2201841) genes were genotyped by PCR-RFLP, the G908R (rs2066844) in CARD15 was determined by direct sequencing.
The association of ATG16L1 T300A with CD was confirmed [P = 0.004, odds ratio (OR) = 1.69, 95% CI: 1.19-2.41], and both IL23R variants were found to represent significant risk for the disease (P = 0.008, OR = 2.05, 95% CI: 1.20-3.50 for rs1004819 AA; P < 0.001, OR = 2.97, 95% CI: 1.65-5.33 for rs2201841 CC). Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD) loci indicated that IL23R, ATG16L1, CARD15 and IBD5 (IGR2198a_1) contribute independently to disease risk. We also analysed the specific combinations by pair of individual ATG16L1, IL23R rs1004819, rs2201841, IGR2198a_1, IGR2096a_1 and CARD15 genotypes for disease risk influence. In almost all cases, the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism. The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status (P < 0.001, OR = 9.15, 95% CI: 2.05-40.74).
The present study suggests a cumulative effect of individual IBD susceptibility loci.
探讨白细胞介素-23 受体（IL23R）（rs1004819 和 rs2201841）、自噬相关 16 样蛋白 1（ATG16L1）（rs2241880）、半胱氨酸蛋白酶募集域蛋白 15（CARD15）基因与 IBD5 基因座在克罗恩病（CD）患者中的相互作用。
对 315 例无血缘关系的 CD 患者和 314 例健康对照者进行基因分型。共检测了 8 个变异的总相互作用和特定基因型组合。IBD5 基因座（IGR2198a_1 rs11739135 和 IGR2096a_1 rs12521868）、CARD15（R702W rs2066845 和 L1007fs rs2066847）、ATG16L1（rs2241880）和 IL23R（rs1004819、rs2201841）基因的变体通过 PCR-RFLP 进行基因分型，CARD15 的 G908R（rs2066844）通过直接测序确定。
证实 ATG16L1 T300A 与 CD 相关（P = 0.004，OR = 1.69，95%CI：1.19-2.41），并且发现两种 IL23R 变体均为疾病的显著危险因素（P = 0.008，OR = 2.05，95%CI：1.20-3.50 用于 rs1004819 AA；P < 0.001，OR = 2.97，95%CI：1.65-5.33 用于 rs2201841 CC）。对炎症性肠病（IBD）基因座的成对相互作用的逻辑回归分析表明，IL23R、ATG16L1、CARD15 和 IBD5（IGR2198a_1）独立于疾病风险。我们还通过个体 ATG16L1、IL23R rs1004819、rs2201841、IGR2198a_1、IGR2096a_1 和 CARD15 基因型对疾病风险影响的组合进行了分析。在几乎所有情况下，与仅携带一种多态性的个体相比，同时携带两种不同易感基因变异的患者的联合风险更高。携带 IL23R rs2201841 纯合基因型与阳性 CARD15 状态的组合发现了最高的 OR（P < 0.001，OR = 9.15，95%CI：2.05-40.74）。
本研究提示个体 IBD 易感性基因座存在累积效应。
