摘要AIM: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.METHODS: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 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.RESULTS: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 onepolymorphism.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).CONCLUSION:The present study suggests a cumulative effect of individual IBD susceptibility loci.