溃疡性结肠炎患者中诱骗受体和护骨素基因多态性及其结肠组织表达水平分析  

Analysis the Association of Ulcerative Colitis with Decoy Receptors and Osteoprotegerin Gene Polymorphisms and Their Colonic Expressions

作　　者：邵晓晓[1] 金颖莉 林芊如 闵全佳 朱浩奇 蒋益[1] Shao Xiaoxiao;Jin Yingli;Lin Qianru(Department of Gastroenterology,The Second Affiliated Hospital of Wenzhou Medical University,Zhejiang 325000,China)

机构地区：[1]温州医科大学附属第二医院消化内科,325000

出　　处：《医学研究杂志》2020年第6期107-113,共7页Journal of Medical Research

基　　金：浙江省自然科学基金资助项目(LY15H030018,LY16H160055,Y17H030011,Y18H030009);浙江省温州市科技局基金资助项目(Y20180637)。

摘　　要：目的拟在浙江省汉族人群中探讨结肠组织中诱骗受体和护骨素基因多态性及其结肠组织表达水平与UC的关系。方法收集56例UC患者和62例性别、年龄相匹配的良性结肠息肉患者作为对照组,采集空腹外周静脉血和结肠组织标本。采用SNaPshot技术检测DcR1(rs12549481)、DcR2(rs1133782)及OPG(rs3102735)的基因多态性。采用反转录实时定量PCR(RT-qPCR)法和免疫组织化学法检测结肠组织中DcR1、DcR2、OPG mRNA及蛋白表达水平。在UC组和对照组之间,以及携带不同基因型的UC患者之间比较结肠组织中DcR1、DcR2、OPG mRNA和蛋白表达水平差异。结果UC组中突变基因型(GA+AA)及突变等位基因(A)频率均显著高于正常对照组(15.18%vs 6.45%,OR=2.595,95%CI:1.073~6.274,P=0.030;28.57%vs 12.90%,OR=2.700,95%CI:1.053~6.926,P=0.035)。UC患者结肠组织中DcR2mRNA和蛋白表达水平均显著低于对照组(4.49±2.29 vs 9.49±4.06,t=8.134,P<0.01;0.180±0.052 vs 0.273±0.069,t=8.322,P<0.01)。携带DcR2(rs1133782)突变基因型(GA+AA)的患者结肠组织中DcR2的mRNA和蛋白表达水平显著高于携带野生纯合子(GG)基因型者(3.64±1.63 vs 6.62±2.35,t=5.43,P<0.01;0.129±0.028 vs 0.198±0.047,t=7.147,P<0.01)。然而,UC组和对照组之间,以及携带DcR1、OPG不同基因型的UC患者之间,DcR1和OPG mRNA和蛋白表达水平差异均无统计学意义(P均>0.05)。结论DcR2(rs1133782)基因突变可能降低UC的发病风险,其机制可能通过降低DcR2 mRNA和蛋白表达水平发挥作用,DcR1(rs12549481)和OPG(rs3102735)基因多态性及其结肠组织表达水平与UC的发病风险无显著关联。Objective To explore the association of ulcerative colitis with decoy receptors and osteoprotegerin gene polymorphisms and their colonic expressions in the Han nationality from Zhejiang province.Methods A total of 56 UC patients and 62 sex-and age-matched controls with benign colonic polyps were randomly recruited.The peripheral fasting venous blood and colonic tissue samples were collected.The polymorphisms of DcR1(rs12549481),DcR2(rs1133782)and OPG(rs3102735)were examined using a SNaPshot method.The mRNA and protein expression levels of DcR1,DcR2 and OPG in colonic tissues were detected by reverse real-time quantitative polymerase chain reaction(RT-qPCR)and immunohistochemistry technique,respectively.In addition,the mRNA and protein expression levels of DcR1,DcR2 and OPG were compared between UC patients with different genotypes.Results The frequencies of mutant allele(A)and genotypes(GA+AA)of DcR2(rs1133782)were significantly higher in UC patients than in the controls(15.18%vs 6.45%,OR=2.595,95%CI:1.073-6.274,P=0.030;28.57%vs 12.90%,OR=2.700,95%CI:1.053-6.926,P=0.035).The expression levels of both DcR2 mRNA and protein were significantly decreased in colonic tissues of UC patients in contrast with the controls(4.49±2.29 vs 9.49±4.06,t=8.134,P<0.01;0.180±0.052 vs 0.273±0.069,t=8.322,P<0.01).Compared with the patients carrying(GG)genotype of DcR2(rs1133782),the expression levels of both DcR2(rs1133782)mRNA and protein were also significantly reduced in those carrying(GA+AA)genotypes(3.64±1.63 vs 6.62±2.35,t=5.43,P<0.01;0.129±0.028 vs 0.198±0.047,t=7.147,P<0.01).However,no significant difference in the mRNA and protein expression levels of DcR1 and OPG were observed between the patients with UC and the controls as well as the patients with UC carrying different genotypes(all P>0.05).Conclusion DcR2(rs1133782)gene mutation may reduce the risk of UC by reducing the mRNA and protein expression levels of DcR2.However,DcR1(rs12549481)and OPG(rs3102735)gene polymorphism and their intestinal tissue expression le

关 键 词：诱骗受体 护骨素 溃疡性结肠炎 基因多态性 结肠组织表达 

分 类 号：R5[医药卫生—内科学]