CAJ | 학술논문

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Chromas 1.62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(x2GMH=4 77,P＜0.05).结论:在观察对象中未发现肿瘤坏死因子α基因启动子-238和-308位点多态性与强直性脊柱炎发病易感性相关,但根据骶髂关节损害程度X射线分级说明肿瘤坏死因子α基因启动子-308位点的多态性对强直性脊柱炎的严重程度有影响. 揹景:腫瘤壞死因子α基因多態性與彊直性脊柱炎髮生與髮展的關繫是近年彊直性脊柱炎遺傳學研究的熱點.目的:探討腫瘤壞死因子α基因啟動子-238和-308位點多態性對彊直性脊柱炎髮病易感性和病變程度的影響.設計:病例-對照觀察.單位:第二軍醫大學長海醫院風濕免疫科.對象:隨機選擇1999-01/2003-12在第二軍醫大學長海醫院風濕免疫科就診的彊直性脊柱炎患者108例,各對象間均無血緣關繫.男女比為5.3:1;年齡13～71(30±12)歲,根據骶髂關節破壞程度X射線片評估為Ⅰ～Ⅳ級.另從解放軍上海血站(長海醫院)隨機選取100名健康獻血者作為對照,年齡19～56(33±9)歲,男女比為4.9:1,參與者均知情同意.方法:每例參與者取外週血,加乙二胺四乙痠A抗凝後進行腫瘤壞死因子-α基因啟動子的聚閤酶鏈反應擴增和純化;對聚閤酶鏈反應產物測序,併用Chromas 1.62軟件展示分析DNA測序結果.②以X射線骶髂關節片分級和腫瘤壞死因子α-308位點(G/C)和(G/A)的對應值評估其對疾病程度的影響.主要觀察指標:以DNA直接測序法對-238和-308位點進行基因分型,併分析基因類型與疾病臨床錶現之間的關繫.結果:①腫瘤壞死因子α-238G/G基因型和-238G/A基因型:彊直性脊柱炎組有106例(98.1%)和2例(1.9%),正常對照組有95例(95.0%)和5例(5.0%),兩組間比較無顯著性差異.②腫瘤壞死因子α-308.1.1(G/G)基因型和-308.1.2(G/A)基因型:彊直性脊柱炎組有89例(82.4%)和19例(17.6%),正常對照組中有85例(85.0%)和14例(14.0%).兩組比較亦無顯著性差異.③根據骶髂關節X射線分級判定疾病嚴重程度與腫瘤壞死因子α-308位點G/G和G/A基因型之間的關繫:彊直性脊柱炎患者X射線片Ⅰ級、Ⅱ級、Ⅲ級和Ⅳ級時,(G/G)型為3/35/40/11例,(G/A)型為1/12/6/0例.兩組差異比較意義顯著(x2GMH=4 77,P＜0.05).結論:在觀察對象中未髮現腫瘤壞死因子α基因啟動子-238和-308位點多態性與彊直性脊柱炎髮病易感性相關,但根據骶髂關節損害程度X射線分級說明腫瘤壞死因子α基因啟動子-308位點的多態性對彊直性脊柱炎的嚴重程度有影響.
배경:종류배사인자α기인다태성여강직성척주염발생여발전적관계시근년강직성척주염유전학연구적열점.목적:탐토종류배사인자α기인계동자-238화-308위점다태성대강직성척주염발병역감성화병변정도적영향.설계:병례-대조관찰.단위:제이군의대학장해의원풍습면역과.대상:수궤선택1999-01/2003-12재제이군의대학장해의원풍습면역과취진적강직성척주염환자108례,각대상간균무혈연관계.남녀비위5.3:1;년령13～71(30±12)세,근거저가관절파배정도X사선편평고위Ⅰ～Ⅳ급.령종해방군상해혈참(장해의원)수궤선취100명건강헌혈자작위대조,년령19～56(33±9)세,남녀비위4.9:1,삼여자균지정동의.방법:매례삼여자취외주혈,가을이알사을산A항응후진행종류배사인자-α기인계동자적취합매련반응확증화순화;대취합매련반응산물측서,병용Chromas 1.62연건전시분석DNA측서결과.②이X사선저가관절편분급화종류배사인자α-308위점(G/C)화(G/A)적대응치평고기대질병정도적영향.주요관찰지표:이DNA직접측서법대-238화-308위점진행기인분형,병분석기인류형여질병림상표현지간적관계.결과:①종류배사인자α-238G/G기인형화-238G/A기인형:강직성척주염조유106례(98.1%)화2례(1.9%),정상대조조유95례(95.0%)화5례(5.0%),량조간비교무현저성차이.②종류배사인자α-308.1.1(G/G)기인형화-308.1.2(G/A)기인형:강직성척주염조유89례(82.4%)화19례(17.6%),정상대조조중유85례(85.0%)화14례(14.0%).량조비교역무현저성차이.③근거저가관절X사선분급판정질병엄중정도여종류배사인자α-308위점G/G화G/A기인형지간적관계:강직성척주염환자X사선편Ⅰ급、Ⅱ급、Ⅲ급화Ⅳ급시,(G/G)형위3/35/40/11례,(G/A)형위1/12/6/0례.량조차이비교의의현저(x2GMH=4 77,P＜0.05).결론:재관찰대상중미발현종류배사인자α기인계동자-238화-308위점다태성여강직성척주염발병역감성상관,단근거저가관절손해정도X사선분급설명종류배사인자α기인계동자-308위점적다태성대강직성척주염적엄중정도유영향.
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-α promoter 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- Ⅳ radiographic 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.ti-coagulated with EDTA. Polymerase chain reaction amplification and purification of the TNF-α promoter region was made and the sequence of polymerase chain reaction products was examined and displayed by Chromas 1.62 softcorresponding 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.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) respecquency of TNF-α promoter gene at positions -308. 1.1(G/G) and - 308.1.2(G/A) alleles was 82.4% (89 cases) and 17.6% (192 cases) respectively in AS group, which was not significantly different compared respectively with 85.0% (85 cases) and 14.0% (14 cases) of the control of sacro-iliac joint damage and the frequency of TNF-α promoter gene at the position of - 308 (G/G) and (G/A): AS patients with(G/G) phenotype who were confirmed of radiographic stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ were observed in 3/35/40/11cases,compared with (G/A) phenotype of 1/12/6/0 cases.The difference was statistically significant (χ2GMH = 4.77, P ＜ 0.05 ).CONCLUSION: Our data suggest that the polymorphisms of TNF-α promoter gene at positions of - 238 and - 308 allele has no association with AS susceptibility, but the polymorphisms of TNF - α promoter gene at the position of -308 might exert great influence on AS according to the radiographic stage of sacro-iliac joint damage.