Genetic variants of IL-33 are associated with clinical phenotypes of inflammatory bowel disease in Han population of southern China

AIM：To investigate whether the single nucleotide polymorphisms (SNPs) of interleukin-33 (IL-33) gene are associated with inflammatory bowel disease (IBD) in the Han population of southern China. METHODS：Eight tag-SNPs were selected from the IL-33 gene using the HapMap database. These tag-SNPs were genotyped in 250 Crohn disease (CD) patients, 115 ulcerative colitis (UC) cases and 622 healthy controls by MALDI-TOF MS assay. RESULTS：No difference of the distribution frequencies of genotypes and alleles between the cases and the controls was observed (P>0.05). Genotype-phenotype analysis suggested that several sites were associated with clinical phenotypes of CD.The T allele of SNP rs10118795 was a protective factor for extra-intestinal manifestation (EIM; P<0.05, OR=0.513, 95% CI： 0.281~0.938), while the CC genotype of SNP rs7025417 (P<0.05, OR=1.363, 95% CI： 1.006~1.846) was a risk factor for EIM. The C allele of rs10118795 decreased the risk for developing perianal lesions (P<0.05, OR=0.480, 95% CI： 0.232~0.994), while the CC genotype of rs10975519 was a risk factor for perianal lesions (P<0.05, OR=2.054, 95% CI： 1.053~4.009). The G allele of rs10975509 increased the risk of upper gastrointestinal CD (P<0.05, OR=3.570, 95% CI： 1.328～9.600), and the A allele of it increased the risk for developing ileocolonic CD (P<0.05, OR=0.613, 95% CI： 0.377~0.996). In the aspect of treatment, the genotypes of rs10118795, rs10975509 and rs7025417 were associated with mucosal healing after infliximab treatment for 30 weeks (P<0.05, P<0.01 and P<0.05). In the UC patients, no significant effect of the selected 8 tag-SNPs on the UC phenotypes was observed. CONCLUSION：Eight polymorphisms of IL-33 do not increase the risk of CD and UC in the Han population of southern China, but some of them have an effect on the clinical phenotypes of CD, and 3 SNPs may be potential markers for prediction of effectiveness of infliximab treatment.