IL-12B基因多态性及单倍型与克罗恩病的关系研究

Association of polymorphisms and haplotypes of IL-12B gene with Crohn's disease

目的 探讨IL-12B基因多态性及单倍型与克罗恩病(CD)的关系。方法 选取94例CD患者(CD组)和106例健康体检者(对照组),采用改良多重高温连接酶检测反应技术检测IL-12B基因2个功能性单核苷酸多态性(SNP)位点rs3212227和rs6887695的等位基因及基因型,用Haploview 4.2软件进行连锁不平衡和单倍型分析,并分析IL-12B基因多态性及单倍型与CD的关系。结果 CD组与对照组比较,该2个IL-12B基因SNP位点的突变等位基因和基因型频率均无统计学差异(均P>0.05)。进一步亚组分析发现回肠型CD组患者rs6887695位点的突变C等位基因和GC+CC基因型频率均明显低于与对照组(28.75%vs 44.34%,P<0.05,OR=0.507,95%CI:0.291~0.882;50.00%vs 71.70%,P<0.05,OR=0.395,95%CI:0.186~0.836);而上述2个位点的等位基因及基因型频率分布在结肠病变(结肠型+回结肠型)CD组患者与对照组间比较均无统计学差异(均P>0.05)。此外,CD患者组内分层比较发现,与结肠病变CD组比较,回肠型CD组患者rs6887695位点的突变C等位基因、GC+CC基因型以及CC基因型频率亦均明显降低(28.75%vs 50.00%,P<0.05,OR=0.404,95%CI:0.218~0.745;50.00%vs 72.22%,P<0.05,OR=0.385,95%CI:0.163~0.908;7.50%vs27.78%,P<0.05,OR=0.150,95%CI:0.037~0.613)。经Haploview 4.2软件分析发现rs3212227和rs6887695 2个SNP位点之间存在中等强度连锁不平衡关系(D′=0.545,r2=0.235),但CD组与对照组比较,各单倍型的频率均无统计学差异(均P>0.05)。结论 IL-12B基因rs6887695位点多态性与CD的临床表型相关,该位点基因突变后可能降低回肠型CD的发病风险。

Objective To investigate the associations of the single nucleotide polymorphisms（SNP） and haplotypes of IL-12 B gene with Crohn＇s disease. Methods Ninety four patients with Crohn＇s disease（CD） and 106 healthy controls were recruited in our study. Two SNPs of IL-12 B（rs3212227 and rs6887695） were examined with the improved multiple ligase detection reaction technique. The analyses of linkage disequilibrium and haplotype were further performed with Haploview 4.2 software. Results There was no significant difference in allele and genotype distribution of IL-12 B gene between CD patients and healthy controls（all P〉0.05）. In the stratified analyses, the mutant allele（C） and genotype（GC＋CC） of IL-12 B（rs6887695） were significantly decreased in ileal CD patients compared to controls（28.75% vs44.34%, OR=0.507, 95%CI： 0.291-0.882, P〈0.05; 50.00% vs 71.70%, OR=0.395, 95% CI： 0.186-0.836, P〈0.05, respectively）. Moreover,The mutant allele（C）, genotype（TG＋GG） and genotype（CC） of IL-12 B（rs6887695） were also significantly decreased in patients with pure ileal CD, as compared to colonic and ileocolonic CD patients（28.75% vs 50.00%, OR=0.404, 95% CI： 0.218-0.745, P〈0.05; 50.00% vs72.22%, OR=0.385, 95%CI： 0.163-0.908, P〈0.05; 7.50% vs 27.78%, OR=0.150, 95%CI： 0.037-0.613, P〈0.05, respectively）. In addition, the two polymorphic loci of IL-12 B gene were in a moderate linkage disequilibrium in our study（D＇=0.545, r2=0.235）. However, the frequency of each haplotype constructed by above two loci was not statistically different between CD patients and the controls（all P〉0.05）. Conclusion IL-12 B polymorphism is associated with the clinic characteristic of CD patient and（rs6887695） mutation might engender the decreased risk of pure ileal Crohn＇s disease.