TRAIL受体家族基因多态性及sTRAIL水平与溃疡性结肠炎的关系  

Associations of Genetic Polymorphisms of TRAIL Receptors Family and the Plasma Levels of sTRAIL with Ulcerative Colitis

作　　者：王建嶂[1] 林李淼[1] 徐昌隆[1] 吴小丽[2] 金捷 丁然 薛战雄[1] 

机构地区：[1]温州医科大学附属第二医院消化内科,325000 [2]温州医科大学附属第一医院消化内科 [3]温州市中心医院消化内科 [4]温州市人民医院消化内科

出　　处：《医学研究杂志》2017年第1期91-97,共7页Journal of Medical Research

基　　金：温州市科技局基金资助项目(Y20130052)

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。Objective The receptor family of tumor necrosis factor - related apoptosis - inducing ligand （TRAIL） comprises death receptors （DR4, DR5 ）, decoy receptors （DeR1, 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） , DcRl（rs12549481） , DcR2 （rs1133782） and OPG （rs3102735） were detected by SNaPshot. Results Under an autoso- mal 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 a- nalysis, 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 pa- tien

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 

分 类 号：R5[医药卫生—内科学]