青海地区回族类风湿关节炎患者抗环瓜氨酸抗体与血清肽酰基精氨酸脱亚氨酶基因多态性关系的研究

Anti-cyclic Citrullinated Peptide Antibody and Serum Peptidylarginine Eiminase Polymorphism in Rheumatoid Arthritis Patients in Qinghai Hui Population

目的探讨青海地区回族类风湿关节炎(RA)患者抗环瓜氨酸多肽(CCP)抗体水平与血清肽酰基精氨酸脱亚氨酶(PADI)基因多态性的关系,及两者在RA发病机制中的意义。方法选择我院风湿科2009年6月—2011年11月住院及门诊回族RA患者63例为病例组,选择同期我院回族健康体检者54例为对照组。采用酶联免疫吸附试验(ELISA法)检测两组受试者抗CCP抗体水平,魏氏法检测红细胞沉降率(ESR),免疫散射比浊法检测C反应蛋白(CRP)和类风湿因子(RF)水平。根据GenBank号NT_004610序列查找PADI4基因多态性位点,即PADI4-94、PADI4-104、PADI4-92,其基因多态性分型采用聚合酶链反应(PCR)产物扩增后收集DNA片段进行测序。采用RA疾病活动评分(DAS28评分)评价病例组患者疾病活动性,HAQ生活质量问卷(HAQ评分)评价其生活质量。结果 (1)两组ESR、CRP水平、抗CCP抗体水平及RF水平比较,差异均有统计学意义(P<0.05)。(2)病例组患者DAS28评分平均为(4.89±0.17)分,HAQ评分平均为(8.07±1.03)分。(3)PADI4-94位点的基因型为A/A、G/G、A/G,PADI4-104位点为A/A、G/G、A/G,PADI4-92位点为C/C、G/G、G/C。3个位点不同基因型RA患者抗CCP水平比较,差异均无统计学意义(P>0.05)。(4)Pearson相关分析显示,RA患者抗CCP抗体水平与DAS28评分(r=0.25,P=0.018)、HAQ评分(r=0.22,P=0.04)及ESR(r=0.81,P=0.001)均呈正相关,与CRP、RF无相关性。结论青海地区回族RA患者血清抗CCP抗体水平高于回族健康人群,并与DAS28评分、HAQ评分及ESR呈正相关,提示抗CCP抗体可作为评价回族RA患者疾病活动度的指标,PADI4基因多态性可能与抗CCP抗体形成无相关性。

Objective To investigate the anti-cyclic citrullinated peptide（CCP）antibody levels in patients with rheumatoid arthritis and explore its relationship with serum peptide arginine eiminase polymorphism.Methods The serum anti-CCP antibody level in 63 RA patients and 54 healthy controls was determined with enzyme linked immunosorbent assay（ELISA）.Erythrocyte sedimentation rate（ESR）was measured with Westergren method.C-reactive protein（CRP）and rheumatoid factor（RF）were determined with immune scatter turbidimetry.RA PADI4-94,PADI4-104 and PADI4-92 gene polymorphism sites were identified in GenBank（NT_004610）.The polymorphism types were amplified with polymerase chain reaction and the DNA fragments were sequenced.Results There were significant differences between the two groups compared with ESR,CRP,anti-CCP and RF levels（P0.05）.The average disease activity score（DAS28）was（4.89±0.17）,and the quality of life score（HAQ）was（8.07±1.03）.The genotypes in RA PADI4-94 were A/A,G/G,and A/G,in PADI4-104 were A/A,G/G,and A/G,and in PADI4-92 were C/C,G/G,and G/C.The CCP level had no significant differences among these types（P0.05）.Pearson′s correlation analysis showed that the anti-CCP antibody level was positively correlated with DAS28（r=0.25,P=0.018）,HAQ（r=0.22,P=0.04）,and ESR（r=0.81,P=0.001）;However,no correlation was observed between the anti-CCP antibody and CRP and RF.Conclusion The anti-CCP antibody level is high among RA patients than the healthy individuals among Hui population and is positively correlated with DAS28 scores,HAQ scores,and ESR.It may be a useful indicator for assessing the disease activity in population.The development of PADI4 polymorphism may be not associated with the anti-CCP antibody.