肿瘤坏死因子相关凋亡诱导配体基因多态性及单倍型与溃疡性结肠炎易感性相关性研究

The genetic polymorphisms of tumor necrosis factor related apoptosisinducing ligand are correlated with the susceptibility to ulcerative colitis

[目的]探讨肿瘤坏死因子相关凋亡诱导配体(Trail)(G1525A、C1595T)基因多态性及单倍型与溃疡性结肠炎(UC)易感性的关系。[方法]收集252例UC患者和775例正常对照者(HC),采用直接测序法检测Trail(G1525A、C1595T)等位基因及基因型,并做单倍型分析。[结果]与HC组相比,UC组Trail G1525A变异等位基因(A)和基因型(GA+AA)的频率明显减低(35.52%VS 55.94%,P<0.01;41.27%VS 79.74%,P<0.01);TrailC1595T变异基因型(CT+TT)的频率UC组亦明显降低(70.23%VS 80.52%,P<0.01)。单倍型分析发现Trail(G1525A、C1595T)完全连锁(D’=0.979,r2=0.810)。与HC组比较,GC、GT单倍型UC组明显增高(46.56%VS 36.77%,P<0.01;13.36%VS 7.54%,P<0.01);而AC、AT单倍型明显降低(0.64%VS 10.22%,P<0.01;39.44%VS 45.47%,P<0.01)。[结论]Trail(G1525A、C1595T)基因多态性及单倍型与UC易感性相关,此2位点基因变异对UC可能具有保护作用。

[Objective]To investigate the associations of the polymorphisms and haplotypes in tumor necrosis factor related apoptosis-inducing ligand （Trail）（G1525A, C1595T）genes with the susceptibility to ulcerative colitis（UC）. [Methods]A total of 252 consecutive patients with UC, and 775 healthy controls（HC）were recruited in this study. Two single nucleotide polymorphisms in Trail（G1525A, C1595T）genes were determined using direct sequencing methods. Haptotype a- nalysis was also made in all study subjects. [Results]In contrast with the HC, the variant allele （A）and genotype（GAff-AA）in Trail G1525A gene were significantly diminished in UC patients （35.52% VS 55.94%, P〈0. 01;41.27% VS 79.74%, P%0.01, respectively）. The same results were drawn for the variant genotype（CT＋TT）in Trail C1595T gene（70.23% VS 80.52%, P% 0.01）. In haplotype analysis,Trail（G1525A, C1595T）were shown to be in complete linkage dise- quilihrium（D＇ =0. 979, r2 = 0. 810）. The frequencies of GC and GT haplotypes were significantly higher in UC patients than in the HC（46.56% VS 36.77%,P〈0.01; 13.36G VS 7.54%,P% 0. 01, respectively）. Both AC and AT haplotype, nevertheless, were significantly lower in UC patients（0.64% VS 10. 22%,P〈0. 01;39.44% VS 45.47%, P〈0. 01, respectively）. [Conelusion] The polymorphisms and haplotypes in Trail（G1525A, C1595T）genes are correlated with the susceptibility to UC. The genetic mutation of Trail（G1525A, C1595T）may play a protective role in UC patients.