肿瘤坏死因子α基因多态性对强直性脊柱炎发病易感性和临床病变程度的影响(英文)  

Tumor necrosis factor alpha gene polymorphisms in ankylosing spondylitis:associations with clinical disease progression and disease susceptibility

作　　者：韩星海[1] 陈蕊雯[2] 段世伟[3] 杨波[1] 蔡青[1] 林懿[2] 孙树汉[2] 

机构地区：[1]解放军第二军医大学长海医院风湿免疫科,上海市200433 [2]解放军第二军医大学基础医学部医学遗传学教研室,上海市200433 [3]上海交通大学生命科学研究中心,中国科学院营养研究所,上海市200031

出　　处：《中国临床康复》2005年第22期252-254,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：背景:肿瘤坏死因子α基因多态性与强直性脊柱炎发生与发展的关系是近年强直性脊柱炎遗传学研究的热点。目的:探讨肿瘤坏死因子α基因启动子-238和-308位点多态性对强直性脊柱炎发病易感性和病变程度的影响。设计:病例-对照观察。单位:第二军医大学长海医院风湿免疫科。对象:随机选择1999-01/2003-12在第二军医大学长海医院风湿免疫科就诊的强直性脊柱炎患者108例,各对象间均无血缘关系。男女比为5.3∶1;年龄13～71(30±12)岁,根据骶髂关节破坏程度X射线片评估为Ⅰ～Ⅳ级。另从解放军上海血站(长海医院)随机选取100名健康献血者作为对照,年龄19～56(33±9)岁,男女比为4.9∶1,参与者均知情同意。方法:每例参与者取外周血,加乙二胺四乙酸A抗凝后进行肿瘤坏死因子-α基因启动子的聚合酶链反应扩增和纯化;对聚合酶链反应产物测序,并用Chromas1.62软件展示分析DNA测序结果。②以X射线骶髂关节片分级和肿瘤坏死因子α-308位点(G/C)和(G/A)的对应值评估其对疾病程度的影响。主要观察指标:以DNA直接测序法对-238和-308位点进行基因分型,并分析基因类型与疾病临床表现之间的关系。结果:①肿瘤坏死因子α-238G/G基因型和-238G/A基因型:强直性脊柱炎组有106例(98.1%)和2例(1.9%),正常对照组有95例(95.0%)和5例(5.0%),两组间比较无显著性差异。②肿瘤坏死因子α-308.1.1(G/G)基因型和-308.1.2(G/A)基因型:强直性脊柱炎组有89例(82.4%)和19例(17.6%),正常对照组中有85例(85.0%)和14例(14.0%)。两组比较亦无显著性差异。③根据骶髂关节X射线分级判定疾病严重程度与肿瘤坏死因子α-308位点G/G和G/A基因型之间的关系:强直性脊柱炎患者X射线片Ⅰ级、Ⅱ级、Ⅲ级和Ⅳ级时,(G/G)型为3/35/40/11例,(G/A)型为1/12/6/0例。两组差异比较意义显著(χ2GMH=4.77,P<0.05)。结论:在观察对象中未发现肿瘤坏死因子α基�BACKGROUND:The association of tumor necrosis factor alpha (TNF-α) gene polymorphisms with the onset and development of ankylosing spondylitis (AS) has been the focus of studies on AS in the field of genetics. OBJECTIVE:To explore the association of the polymophisms of TNF-αpromoter gene at positions-308 and -238 with AS susceptibility and clinical pathological changes. DESIGN:A case-control study. SETTING:The Rheumatic Immunology Department of Changhai Hospital of the Second Military Medical University of Chinese PLA. PARTICIPANTS:Totally,108 AS patients were recruited from Rheumatic Immunology Department of Changhai Hospital,Second Military Medical University of Chinese PLA from January 1999 to December 2003,they had no kinship.The ratio of men to women was 5.3∶1.They aged from 13 to 71 (30±12) years old,and AS was divided into Ⅰ-Ⅳradiographic stages according to the sacro-iliac joint damage.A total of 100 healthy controls were randomly selected from the blood donators(Shanghai Hospital) who were aged from 19-56 (33±9) years old,and the ratio of men to women was 4.9∶1.Informed consent was obtained from all the subjects. METHODS:①Peripheral blood samples were collected and were anti-coagulated with EDTA.Polymerase chain reaction amplification and purification of the TNF-αpromoter region was made and the sequence of polymerase chain reaction products was examined and displayed by Chromas 1.62 software.②The value of TNF-αat the position -308(G/C)and (G/A)and the corresponding radiographic stage of sacro-iliac joint damage was assessed to investigate the influence of gene polymorphisms on AS. MAIN OUTCOME MEASURES:DNA direct sequencing method was used to detect -238 and -308 allele phenotypes for investigating the association with clinical presentations. RESULTS:①The frequency of TNF-αpromoter gene at positions -238G/G and -238G/A allele was 98.1%(106 cases) and1.9%(2 cases) respectively in AS group and 95.0%(95 cases) and 5.0%(5 cases) respectively in the control group.The difference was not si

关 键 词：脊柱炎 强直性 肿瘤坏死因子 多态现象(遗传学) 基因 疾病易感性 

分 类 号：R73[医药卫生—肿瘤]