强直性脊柱炎与肿瘤坏死因子基因启动子-308位点多态性相关的假设验证(英文)

Hypothetic verification of the correlation between polymorphism in the promoter region-308 of the tumor necrosis factor gene and ankylosing spondylitis

背景:强直性脊柱炎(ankylosingspondylitis,AS)患者中HLA-B27的阳性率在不同报道间有明显差异,这种差别可能由环境因素造成,但也可能受其它HLA或非HLA因素影响,推测另一些分子可能在AS发病中起一定作用。目的:探讨肿瘤坏死因子α(tumornecrosisfactor-α,TNF-α)启动子多态性与AS的相关性。设计:非随机对照实验研究。地点和对象:资料收集地点:同济医学院附属协和医院。对象:选择2000-06/2003-01武汉地区78例AS患者作为研究对象,所有AS患者均符合VanderLinder1984年修改的诊断标准,平均年龄(37.4±12.8)岁,男67例,女11例。对照组为HLA-B27阳性的武汉籍体检健康汉族人52人,平均年龄(39.2±14.4)岁,男44人,女8人。干预:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)对AS患者和HLA-B27阳性健康人群进行TNF启动子多态性分析,采用酶联免疫吸附法(ELISA)检测了患者和正常人群血清TNF-α水平。主要观察指标:AS患者TNF基因启动子区域-308位点基因型与AS的关系。结果:AS患者中为-308.1.1基因型的有61例(78%,61/78),明显高于HLA-B27阳性的健康人(56%,29/52),差异有显著性意义(χ2=6.8,P<0.05);AS患者的-308.1.2和-308.2.2基因型频率分别为20%和1%,低于对照的38%(χ2=9.3,P<0.05)和5.8%(χ2=11.4,P<0.01)。

BACKGROUND:The positive rate of human leucocyte antigen(HLA) B27 in the patient with ankylosing spondylitis(AS) has significant differences among different reports,which might be induced by environment but also could be affected by other HLA or non HIL factors.It is presumed that some other factors might play certain roles in the genesis of AS. OBJECTIVE:To investigate the correlation between the polymorphism in the promoter region of tumor necrosis factor(TNF α) and AS. DESIGN:A non randomised controlled trial. SETTING and PARTICIPANTS:Data collection setting:United Hospital Affiliated to Tongji Medical University.Participants:Totally 78 AS cases were selected from Wuhan Region during June 2000 to January 2003,who were in accordance with diagnostic criteria modified by Van der Linder in 1984,including 67 males and 11 females,of which the mean age was(37.4±12.8) years old.52 HLA B27 positive healthy Wuhan citizens,who were the Han nationality were selected in control group, which included 44 male and 8 female subjects with a mean age of(39.2±14.4) years old. INTERVENTIONS:A Nco I restrictive site polymorphism in the promoter region of the TNF gene was detected by polymerase chain reaction restriction fragment length polymorphisms(PCR RFLP) in both 78 patients with AS and 52 HLA B27 positive healthy controls.Meanwhile,enzyme linked immunosorbent assay(ELISA) was used to assay serum TNF αlevel in both patients and controls. MAIN OUTCOME MEASURES:The relationship between the genotype of 308 promoter region of TNF gene and AS. RESULTS:The 308.1.1 genotype was found in 61/78(78.2%) AS patients,which was significantly higher compared with 29/52(55.8%) of HLA B27 positive healthy subjects(χ2=6.8,P< 0.05).The 308.1.2 and 308.2.2 genotypes in AS patients were 20%and 1%respectively,which were significantly lower than 38%(χ2=9.3,P< 0.05) and 5.8%(χ2=11.4,P< 0.01).The levels of serum TNF α[(15.80±11.20) and 28.00 μg/L] and C reactive protein[(44.1±26.3) and 105.3 ng/L],erythrocyte sedimentation rate(ESR)[(27.7±11.5)and 61.5 mm per hour] and immunoglobulin A[(33.5±19.7) and 29.2 g/L] in the AS patients with the latter two genotypes were significantly higher than that of AS patients with 308.1.1 genotype(t=3.5,2.1,3.1,P< 0.05-0.01). CONCLUSION:The 308.1 allele is more common in patients with AS than in HLA B27 positive normal controls,which implies that the polymorphism in this region of TNF gene is correlated with AS.