高尿酸血症患者G-308A肿瘤坏死因子α基因型及mRNA表达与血尿酸的关系
고뇨산혈증환자G-308A종류배사인자α기인형급mRNA표체여혈뇨산적관계
Association of tumor necrosis factor-alpha gene of G-308A genotype and mRNA expression with serum uric acid in hyperuricemic patients
  • 万方数据
    中国组织工程研究与临床康复 중국조직공정연구여림상강복
    JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH
    2007年 30期 6092-6096 ,共5页

    王颜刚%陈新焰%许凤%陆付耳

    왕안강%진신염%허봉%륙부이

    高尿酸血症%尿酸/血液%肿瘤坏死因子α%多态现象%C反应蛋白质 高尿痠血癥%尿痠/血液%腫瘤壞死因子α%多態現象%C反應蛋白質
    고뇨산혈증%뇨산/혈액%종류배사인자α%다태현상%C반응단백질
    背景:高尿酸血症作为代谢综合征的组成成分,其介导炎症的作用日益引起关注.目前,肿瘤坏死因子α启动子区-308 A取代G(G-308A肿瘤坏死因子α)与代谢综合症的关系还存在争议.目的:探讨高尿酸血征患者G-308A肿瘤坏死因子α基因型分布与肿瘤坏死因子α mRNA表达及C-反应蛋白浓度的关系.设计:以高尿酸血症患者为研究对象、正常人为对照组,进行对比观察.单位:华中科技大学同济医学院附属同济医院.对象:在5 003名健康查体中筛选188例高尿酸血症患者、51名健康者.高尿酸血症患者中单纯高尿酸血症40例,高尿酸血症并脂代谢紊乱42例,高尿酸血症并脂代谢紊乱和高血压80例,痛风26例(在实验开始前的1周,停用别嘌呤醇)方法:采用聚合酶链反应扩增后Ncol消化法,电泳后检查G-308A肿瘤坏死因子α基因型分布.采用反转录聚合酶链反应半定量法,观察肿瘤坏死因子αmRNA表达情况.采用高灵敏酶联免疫吸附双抗体夹心法测定血清C-反应蛋白浓度.采用尿酸氧化酶法测定血尿酸.胰岛素抵抗指数采用稳态模型评估法.主要观察指标:①基因型频率Hardy-Weinberg平衡检验结果.②在高尿酸血症中G-308A肿瘤坏死因子α基因型分布和肿瘤坏死因子α mRNA表达的变化.③G-308A肿瘤坏死因子α基因型AA+GA组和GG组肿瘤坏死因子αmRNA表达量及其他指标的变化.④多元逐步回归分析.结果:患者188例、正常人51例全部进入结果分析.①239例被研究者G-308A肿瘤坏死因子α基因型分布符合Hardy-Weinberg平衡.②由于人群AA型基因分布频率少,因此采用AA+GA与GG 较.结果显示在高尿酸血症伴脂代谢紊乱和高血压患者中AA+GA分布(30%)高于对照组(12%)(P＜0.05);其余各组之间无明显差异.③肿瘤坏死因子α mRNA表达量和血清C-反应蛋白浓度痛风组＞高尿酸血症伴脂代谢紊乱和高血压组＞高尿酸血症伴脂代谢紊乱组＞单纯高尿酸血症组,均明显高于对照组(P＜0.05～0.01);其中高尿酸血症伴脂代谢紊乱和高血压组以及痛风组肿瘤坏死因子α mRNA表达量高于单纯高尿酸血症组(P＜0.05～0.01).AA+GA组腰围与臀围比值、收缩压、舒张压、血尿酸、三酰甘油、肿瘤坏死因子α mRNA表达量和血清C-反应蛋白浓度明显高于GG型组(P=0 05～0.01).④调整性别、年龄、收缩压、舒张压、空腹血糖、体质量指数、总胆固醇、高密度胆固醇后.多元逐步回归分析显示三酰甘油、血尿酸和肿瘤坏死因子α308 A携带者与肿瘤坏死因子α mRNA表达量有关;并显示腰臀比、血尿酸和肿瘤坏死因子α mRNA表达量与C-反应蛋白浓度变化相关.结论:高尿酸血症个体中肿瘤坏死因子α 308A携带者的基因型与肿瘤坏死因子α表达和血浆C-反应蛋白水平有关.
    배경:고뇨산혈증작위대사종합정적조성성분,기개도염증적작용일익인기관주.목전,종류배사인자α계동자구-308 A취대G(G-308A종류배사인자α)여대사종합증적관계환존재쟁의.목적:탐토고뇨산혈정환자G-308A종류배사인자α기인형분포여종류배사인자α mRNA표체급C-반응단백농도적관계.설계:이고뇨산혈증환자위연구대상、정상인위대조조,진행대비관찰.단위:화중과기대학동제의학원부속동제의원.대상:재5 003명건강사체중사선188례고뇨산혈증환자、51명건강자.고뇨산혈증환자중단순고뇨산혈증40례,고뇨산혈증병지대사문란42례,고뇨산혈증병지대사문란화고혈압80례,통풍26례(재실험개시전적1주,정용별표령순)방법:채용취합매련반응확증후Ncol소화법,전영후검사G-308A종류배사인자α기인형분포.채용반전록취합매련반응반정량법,관찰종류배사인자αmRNA표체정황.채용고령민매련면역흡부쌍항체협심법측정혈청C-반응단백농도.채용뇨산양화매법측정혈뇨산.이도소저항지수채용은태모형평고법.주요관찰지표:①기인형빈솔Hardy-Weinberg평형검험결과.②재고뇨산혈증중G-308A종류배사인자α기인형분포화종류배사인자α mRNA표체적변화.③G-308A종류배사인자α기인형AA+GA조화GG조종류배사인자αmRNA표체량급기타지표적변화.④다원축보회귀분석.결과:환자188례、정상인51례전부진입결과분석.①239례피연구자G-308A종류배사인자α기인형분포부합Hardy-Weinberg평형.②유우인군AA형기인분포빈솔소,인차채용AA+GA여GG 교.결과현시재고뇨산혈증반지대사문란화고혈압환자중AA+GA분포(30%)고우대조조(12%)(P＜0.05);기여각조지간무명현차이.③종류배사인자α mRNA표체량화혈청C-반응단백농도통풍조＞고뇨산혈증반지대사문란화고혈압조＞고뇨산혈증반지대사문란조＞단순고뇨산혈증조,균명현고우대조조(P＜0.05～0.01);기중고뇨산혈증반지대사문란화고혈압조이급통풍조종류배사인자α mRNA표체량고우단순고뇨산혈증조(P＜0.05～0.01).AA+GA조요위여둔위비치、수축압、서장압、혈뇨산、삼선감유、종류배사인자α mRNA표체량화혈청C-반응단백농도명현고우GG형조(P=0 05～0.01).④조정성별、년령、수축압、서장압、공복혈당、체질량지수、총담고순、고밀도담고순후.다원축보회귀분석현시삼선감유、혈뇨산화종류배사인자α308 A휴대자여종류배사인자α mRNA표체량유관;병현시요둔비、혈뇨산화종류배사인자α mRNA표체량여C-반응단백농도변화상관.결론:고뇨산혈증개체중종류배사인자α 308A휴대자적기인형여종류배사인자α표체화혈장C-반응단백수평유관.
    BACKGROUND: Hyperuricemia (HUA), serving as a component of metabolic syndromes (MS), has a major regulatory role in inflammatory responses. However, the correlation between G-308A tumor necrosis factor-α (TNF-α) and MS is still controversial.OBJECTIVE: To study the correlation among G-308A TNF-α genotype distribution, TNF-α mRNA expression and C-reactive protein (CRP) in patients with HUA.DESrGN: Patients with HUA were selected as the subjects, while normal peoplewere taken as the controls.SETTING: Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology.PARTICIPANTS: Subjects were selected from 5 003 people, including 188 patients with HUA and 51 healthy people.Patients with HUA included 40 patients with simple HUA, 42 patients with HUA and dyslipidemia, 80 patients with HUA and dyslipidemia and hypertension, and 26 patients with gout (administration of allopurinol was stopped at one week before the experiment).METHODS: TNF-α gene promoter G-308A genotype was determined by using PCR application followed by Nco/digestion.TNF-α mRNA expression was studied by RT-PCR with semi-quantitative analysis. Antibody sandwich method and enzyme linked immunosorbent assay (ELISA) were adopted to determine the CRP concentration. And the serum uric acid was measured by uricase method, while the insulin resistance index (IRI) was evaluated with homeostasis model.MArN OUTCOME MEASURES: ① Hardy-Weinberg equilibrium test of genotypic frequency. ② Changes in distribution of G-308A TNF-α genotypes and TNF-α mRNA expression in patients with HUA. ③ Changes in TNF-α mRNA expression and other parameters in G-308A TNF-α AA+GA and GG groups. ④ Multiple stepwise regression analysis.RESULTS: A total of 188 patients and 51 normal people were involved in the analysis of results. ① G-308A TNF-α genotypes distribution in 239 enrolled subjects accorded with Hardy-Weinberg equilibrium. ② AA+GA was compared with GG due to lower frequency of AA in population. The results revealed the HUA with dyslipidemia and hypertension group displayed a greater prevalence in G-308A TNF-α AA+GA genotype (30%) than that in the control group (12%) (P ＜ 0.05),while there were no significant differences among other groups. ③ TNF-α mRNA expression and CRP concentration were the highest in the gout group, and HUA accompanied by dyslipidemia and hypertension group listed the second,and then was the HUA and dyslipidemia group, while simple HUA group listed the last, all of which were higher than those in the normal control group (P ＜ 0.05-0.01). TNF-α mRNA expression in HUA accompanied by dyslipidemia and hypertension group, gout group was higher than that in the normal control group (P ＜ 0.05-0.01). The WHR, SBP, DBP,serum uric acid, triglycerides, TNF-α mRNA expression and CRP concentration in AA+GA group were remarkably higher than those in the GG group (P ＜ 0.05-0.01). ④ After adjustment of age, gender, systolic pressure, diastolic pressure,fasting blood glucose, and multiple variable linear stepwise regression showed that triglycerides, uric acid, TNF-α 308 A carrier were related with quantityof TNF-α mRNA expression. Meanwhile, the uric acid concentration, WHR and the quantity expression of TNF-α were significantly in positive association with CRP concentration.CONCLUSTON:The genotype of TNF-α 308 A carriers is associated with TNF-α expression and plasma CRP levels in HUA patients.
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