IL-33基因单核苷酸多态性与中国南方汉人炎症性肠病临床表型相关

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

目的：探讨白细胞介素33（IL-33）基因单核苷酸多态性（SNP）与中国南方汉人炎症性肠病（IBD）的关系。方法：通过HapMap数据库筛选出IL-33基因8个SNP序列标签；对250例克罗恩病（CD）患者、115例溃疡性结肠炎（UC）患者及622名健康对照采用MALDI—TOFMS技术进行基因分型检测。结果：8个SNP位点的基因型及等位基因频率在病例（包括CD及UC）及对照组中无明显差异（P〉0．05）。基因型-临床表型分析发现多个SNP位点与CD部分临床表型相关：rs10118795T等位基因是肠外表现的保护因素（P〈0．05，OR=0．513，95％CI：0．281～0．938），而rs7025417 CC基因型是肠外表现的危险因素（P〈0．05，OR=1．363，95％CI：1．006～1．846）；rs10118795C等位基因降低肛周病变风险（P〈0．05，OR=0．480，95％CI：0．232～0．994），而rs10975519 CC基因型增加肛周病变风险（P〈0．05，OR=2．054，95％CI：1．053～4．009）；rs10975509G等位基因是上消化道型CD的危险因素（P〈0．05，OR=3．570，95％CI：1．328～9．600），且其A等位基因携带者发生回结肠型CD的风险增加（P〈0．05，OR=0．613，95％CI：0．377～0．996）；在治疗方面，rs10118795、rs10975509和rs7025417基因型均与CD患者英夫利昔单抗治疗后30周黏膜愈合相关（P〈0．05，P〈0．01，P〈0．05）。UC患者中，未发现这8个SNP位点影响其临床表型（P〉0．05）。结论：本研究中IL-33基因8个SNP位点不增加中国南方人群CD及UC发病风险，但部分位点影响CD的临床表型，某些SNP位点可能成为预测英夫利昔单抗疗效的标志物。

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 rsl0118795 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 ElM. The C allele of rs 10118795 decreased the risk for developing perianal lesions （ P 〈 0. 05, OR = 0. 480, 95 % CI ： 0. 232 ～ 0. 994 ）, while the CC genotype of rs 10975519 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 ileoeolonic 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 he potential markers for prediction of effectiveness of infliximab treatment.