护骨素和核因子KB活化因子受体配体基因多态性与类风湿关节炎的相关性研究  

Association of single nuclear polymorphism of nuclear factor-KB-activating factor receptor ligand/osteopro- tegerin in patients with rheumatoid arthritis

作　　者：沈晓潆[1] 邓娟[1] 徐胜前[1] 刘童[1] 装必伟[1] 潘发明[2] 徐建华[1] 

机构地区：[1]安徽医科大学第一附属医院风湿科,合肥230022 [2]安徽医科大学公共卫生学院流行病与卫生统计学系

出　　处：《中国医药》2013年第9期1267-1270,共4页China Medicine

摘　　要：目的探讨护骨素（OPG）基因rs2073618、rs3102735位点和核因子KB活化因子受体配体（RANKL）基因rs2277438位点单核苷酸多态性（SNP）及其外周血水平对类风湿关节炎（RA）患者疾病活动性及骨侵蚀的影响。方法采用连接酶检测反应方法检测101例RA患者OPG基因rs2073618、rs3102735位点和RANKL基因rs2277438位点SNP，ELISA法测定其外周血OPG和RANKL水平，采用Sharp评分评价其双手x线骨侵蚀。结果OPG基因rs2073618位点表达为纯合型RA患者（60例）比杂合型患者（40例）的关节压痛数（13±7比10±6，t=2．154，P=0．034）、关节压痛指数（19±11比13±9，t=2．318，P=0．023）、VAS评分（5．7±1．9比4．8±1．8，t=2．481，P=0．015）明显升高（P〈0．05）；RA患者OPG基因rs3102735位点SNP与其外周血OPG水平、病情活动性指标及Sharp评分无关（P〉0．05）。RANKL基因rs2277438位点表达为纯合型RA患者（62例）和杂合型（39例）间病情活动性指标比较差异无统计学意义（P〉0．05）；但杂合型RA患者外周血RANKL水平较纯合型明显升高（139±152比80±38，￡=2．152，P=0．038）、双手x线Sharp评分亦明显高于纯合型（68±66比40±45，t=2．194，P=0．032）。多元线性回归分析显示，RA患者Sharp评分与病程（卢=0．725，t=9．078，P〈0．01）、外周血RANKL／OPG比值（卢=0．166，t=2．104，P=0．039）、年龄（口=一0．179，t=2．274，P=0．026）呈直线相关（R。=0．570，F=33．137，P〈0．01）。结论OPG基因rs2073618位点SNP与RA患者的病情活动性有关，纯合型患者的病情更重；RANKL基因rs2277438位点SNP与RA患者骨侵蚀相关，杂合型患者外周血RANKL水平更高，骨侵蚀更重。Objective To investigate the influence of single-nuclear polymorphism （SNP） in RANKL, OPG gene and serum level of nuclear factor-KB-activating factor receptor ligand （RANKL） and osteoprotegerin （OPG） on disease activity and hone erosion in rheumatoid arthritis （RA）. Methods We studied 3 SNPs in the genes of OPG （2 SNP： rs2073618, rs3102735） and RANKL （1 SNP： rs2277438） by ligase detection reactions from 113 RA. Serum level of OPG and RANKL were detected meanwhile. All the clinical and laboratory factors of RA were recorded in detail, and the radiographic changes in both hands of RA were assessed by Sharp＇ method. Results Compared to patients with the OPG-rs2073618 heterozygotic type （n = 40）, those with homozygotic type （ n = 60 ） had obviously worse joint function including tender joint counts （ 13 ＋ 7 vs 10 ＋ 6, t = 2. 154, P = 0. 034 ）, tender joint index（ 19 ~ 11 vs 13 ~ 9, t = 2. 318, P = 0.023 ） and VAS score （ 5.7 ~ 1.9 vs 4.8 ＋ 1.8, t = 2. 481, P = 0.015 ）. The additional SNP of OPG rs3102735 neither had conspicuous difference in serum OPG, disease ac- tivity nor bone erosion（P 〉 0.05 ）. The patients with the RANKL-rs2277438 heterozygotic type had significantly ele- vated serum level of RANKL（ 139 ＋ 152 vs 80 ＋ 38, t = 2. 152, P = 0. 038 ） and higher Sharp score （68 ~ 66 vs 40 ~45, t = 2. 194, P = 0. 032）, compared to those with homozygotic type. However, there was no significantly difference in disease activity （ P 〉 0.05 ）. Multivariate linear regression showed that and disease duration （fl = 0. 725, t = 9. 078, P 〈 0.01 ）, ratio of RANKL/OPG in peripheral blood（fl = 0. 166, t = 2. 104, P = 0. 039） and age（fl = -0. 179, t = 2. 274, P = 0. 026） were the eontrubutors for Sharp score（R2 = 0. 570, F = 33. 137, P 〈 0.01 ）. Conclusions OPG gene SNP rs2073618 may have an influence on disease activity in RA patients; pa- tients with homozygotic type have more severe disease activity. RANKL gene SNP rs2277438 tend

关 键 词：类风湿关节炎 核因子KB活化因子受体配体 护骨素 单核苷酸多态性 骨侵蚀 

分 类 号：R593.22[医药卫生—内科学]