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溃疡性结肠炎患者中肿瘤坏死因子相关凋亡诱导配体基因多态性及单倍型分析

The analysis of genetic polymorphisms and haplotype of the Trail gene in the patients with ulcerative colitis

摘要:

目的 探讨肿瘤坏死因子相关凋亡诱导配体(Trail)基因多态性及单倍型与溃疡性结肠炎(UC)的关系.方法 收集UC患者331例,健康对照者832名,PCR扩增Trail目的基因后,直接测序检测Trail基因3非编码区(G1525A/G1588A/C1595T)三种单核苷酸多态性,并分析Trail单倍型与UC的关系.结果 与对照组相比较,Trail G1525A突变等位基因A和基因型GA+ AA的频率在UC组中明显降低(P值均<0.01);UC组Trail G1588A和C1595T两位点突变等位基因A和T的频率明显低于对照组,且差异有统计学意义(P值均<0.01).轻和中度UC患者Trail C1595T突变等位基因T和CT+ TT基因型频率为49.15%和64.51%,重度UC患者分别为72.37%和84.21%,两组比较差异均有统计学意义(OR值分别=2.710和2.935,95%CI:1.598~4.596和1.188~7.249,P值均<0.05).重度UC患者Trail G1525A突变等位基因A的频率为48.69%,较轻和中度UC患者(35.16%)增加(OR=1.750,95%CI:1.082~2.830,P=0.021).UC组中AAT单倍型频率显著低于对照组(43.09%比58.41%,95%CI:1.549~2.229,P<0.01);GAT单倍型频率在UC组中明显增高(10.15%比0.18%,95%CI:0.005~0.051,P<0.01).结论 Trail基因多态性及单倍型与UC易感性密切相关.

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abstracts:

Objective To explore the association between genetic polymorphisms and haplotypes of tumor necrosis factor-related apoptosis inducing ligand (Trail) and ulcerative colitis (UC).Methods A total of 331 patients with UC and 832 age and sex-matched healthy controls were collected.After Trail gene was amplified by PCR,the genetic polymorphisms of three single nucleotides (G1525A/G1588A/C1595T) in 3' non coding regions of Trail gene were examined by direct sequencing.The relation between Trail haplotype and UC was analyzed.Results Compared with control group,the frequencies of variant allele A and genotype GA+ AA in Trail G1525A were significantly lower in UC group (both P<0.01).The frequencies of variant allele A and T in Trail G1588A and C1595T were also significantly lower in UC group than that of control group,and the difference was statistically significant (both P < 0.01 ).In mild and moderate UC patients,the frequencies of variant allele T and CT+TT in Trail C1595T were 49.15% and 64.51%,in severe UC patients were 72.37% and 84.21%,and the differences were significant between the two groups (OR=2.710 and 2.935,95%CI:1.598~4.596 and 1.188~7.249,all P <0.05).In severe UC patients,the frequency of variant allele A in Trail G1525A was 48.69%,which was higher than that of mild and moderate patients (35.16%,OR=1.750,95%CI:1.082~2.830,P=0.021).In UC group,the frequency of AAT haplotype was significantly lower than that of controls (43.09% vs 58.41%,P<0.01).The frequency of GAT haplotype was significantly higher in UC group (10.15%vs 0.18%,95% CI:0.005 ~ 0.051,P< 0.01).Conclusion The genetic polymorphisms and haplotypes of Trail (G1525A/G1588A/C1595T) gene may be closely correlated with the susceptibility to UC.

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作者: 蒋益 [1] 裴继华 [1] 林李淼 [1] 徐昌隆 [1] 王建嶂 [1] 申苏建 [1] 薛战雄 [1]
期刊: 《中华消化杂志》2011年31卷12期 812-816页 ISTICPKUCSCD
栏目名称: 论著
DOI: 10.3760/cma.j.issn.0254-1432.2011.12.006
发布时间: 2012-03-06
基金项目:
温州市科技局
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