TRAIL受体家族基因多态性及sTRAIL水平与溃疡性结肠炎的关系
投稿时间:2016-04-28  修订日期:2016-05-24  点此下载全文
引用本文:王建嶂,林李淼,徐昌隆,吴小丽,金捷,丁然,薛战雄.TRAIL受体家族基因多态性及sTRAIL水平与溃疡性结肠炎的关系[J].医学研究杂志,2017,46(1):91-97
DOI: 10.11969/j.issn.1673-548X.2017.01.026
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作者单位E-mail
王建嶂 325000 温州医科大学附属第二医院消化内科  
林李淼 325000 温州医科大学附属第二医院消化内科  
徐昌隆 325000 温州医科大学附属第二医院消化内科  
吴小丽 325000 温州医科大学附属第一医院消化内科  
金捷 325000 温州市中心医院消化内科  
丁然 325000 温州市人民医院消化内科  
薛战雄 325000 温州医科大学附属第二医院消化内科 xuezhanxiong@126.com 
基金项目:温州市科技局基金资助项目(Y20130052)
中文摘要:目的 肿瘤坏死因子相关凋亡诱导配体(TRAIL)的受体家族包括死亡受体(DR4、DR5),诱骗受体(DcR1、DcR2)及护骨素(OPG)。研究显示TRAIL 3'非翻译区基因多态性与溃疡性结肠炎(UC)的易感性相关,由于TRAIL各受体间的平衡及相互作用是调节靶细胞对TRAIL诱导凋亡敏感度的关键因素,因此本研究将进一步探讨TRAIL受体家族基因多态性与UC的关系。方法 收集146例UC患者和247例正常对照者,采用微测序技术检测DR4(rs20575、rs13278062)、DR5(rs1047266)、DcR1(rs12549481)、DcR2(rs1133782)及OPG(rs3102735)6种单核苷酸多态性。结果 在显性模型中,与对照组相比,UC组中DR4(rs20575)的突变等位基因(G)和基因型(CG+GG)频率均增高(4.79% vs 1.62%,P=0.009;8.22% vs 3.24%,P=0.030),而DcR2(rs1133782)的突变基因型(GA+AA)频率降低(10.27% vs 18.22%,P=0.034)。采用隐性模型分析,UC组中OPG(rs3102735)的突变等位基因(T)和基因型(TT)频率均显著高于对照组(86.99% vs 80.9%,P=0.029;76.03% vs 66.40%,P=0.044)。经非条件Logistic回归分析,与轻中度患者相比,重度UC患者中DR4(rs20575)的突变等位基因(G)和基因型(CG+GG)频率均显著增高(15.00% vs 3.17%,P=0.001;25.00% vs 5.56%,P=0.003),而DR4(rs13278062)的突变基因型(T)和基因型(GT+TT)及OPG(rs3102735)突变等位基因(T)频率均显著降低(17.50% vs 33.73%,P=0.040;30.00% vs 59.22%,P=0.014;75.00% vs 88.89%,P=0.015)。此外,本研究还发现,UC组中sTRAIL水平显著高于对照组。结论 DR4(rs20575)、DcR2(rs1133782)及OPG(rs3102735)基因多态性与UC相关,DR4(rs20575、rs13278062)及OPG(rs3102735)基因突变可能影响UC疾病严重程度。此外,本研究还发现血浆sTRAIL水平与UC相关,提示TRAIL及其受体所构成的凋亡途径可能与UC相关。
中文关键词:溃疡性结肠炎  TNF相关凋亡诱导配体  受体  基因多态性
 
Associations of Genetic Polymorphisms of TRAIL Receptors Family and the Plasma Levels of sTRAIL with Ulcerative Colitis
Abstract:Objective The receptor family of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) comprises death receptors (DR4, DR5), decoy receptors (DcR1, DcR2) and osteoprotegerin (OPG). It had been reported that the polymorphisms of 3' untranslated region in TRAIL gene were correlated with ulcerative colitis (UC). The balance and interaction between each member of the TRAIL receptor family were demonstrated to have a crucial impact on the sensitivity of target cells to apoptosis. Thus the present study aimed to further analyze the association of UC with the genetic polymorphisms of TRAIL receptors. Methods A total of 146 UC patients and 247 controls were recruited in this study. The six single nucleotide polymorphisms of DR4 (rs20575, rs13278062), DR5 (rs1047266), DcR1 (rs12549481), DcR2 (rs1133782) and OPG (rs3102735) were detected by SNaPshot. Results Under an autosomal dominant model, the frequencies of mutant allele (G) and genotype (CG+GG) of DR4 (rs20575) were higher in UC patients than in the controls (4.79% vs 1.62%, P=0.009; 8.22% vs 3.24%, P=0.030, respectively). However, the mutant genotype (GA+AA) of DcR2 (rs1133782) was decreased in UC patients compared to the controls (10.27% vs 18.22%, P=0.034). Under a recessive model, the frequencies of mutant allele (T) and homozygote (TT) of OPG (rs3102735) were significantly higher in UC patients than in the controls (86.99% vs 80.90%, P=0.029;23.97% vs 33.60%, P=0.044, respectively). By unconditional Logistic regression analysis, compared to patients with mild and moderate UC, the frequencies of mutant allele (G) and genotype (CG+GG) in DR4 (rs20575) were significantly higher in patients with severe UC (15.00% vs 3.17%, P=0.001; 25.00% vs 5.56%, P=0.003, respectively). Nevertheless, the mutant allele (T) and genotype (GT+TT) of DR4 (rs13278062) were significantly decreased in patients with severe UC (17.50% vs 33.73%, P=0.040; 30.00% vs 59.22%, P=0.014, respectively). The same result was obtained for the mutant allele (T) of OPG (rs3102735) (75.00% vs 88.89%, P=0.015). Conclusion The genetic polymorphisms of DR4 (rs20575), DcR2 (rs1133782) and OPG (rs3102735) were associated with UC. The mutations of DR4 (rs20575) and (rs13278062) as well as OPG (rs3102735) might influence the severity of UC in the patients. In addition, the plasma levels of sTRAIL were significantly higher in the UC patients than those in the controls. Our findings strongly implicated that the apoptotic pathway formed by TRAIL and its receptors might play a pivotal role in UC.
keywords:Ulcerative colitis  TNF-related apoptosis-inducing ligand  Receptor  Genetic polymorphism
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