CAJ | 학술논문

目的探讨护骨素(OPG)基因rs2073618、rs3102735位点和核因子κB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,EUSA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,t=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(β=0.725,t=9.078,P＜0.01)、外周血RANKL/OPG比值(β=0.166,t=2.104,P=0.039)、年龄(β=-0.179,t=2.274,P=0.026)呈直线相关(R2=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.
목적 탐토호골소(OPG)기인rs2073618、rs3102735위점화핵인자κB활화인자수체배체(RANKL)기인rs2277438위점단핵감산다태성(SNP)급기외주혈수평대류풍습관절염(RA)환자질병활동성급골침식적영향.방법 채용련접매검측반응방법검측101례RA환자OPG기인rs2073618、rs3102735위점화RANKL기인rs2277438위점SNP,EUSA법측정기외주혈OPG화RANKL수평,채용Sharp평분평개기쌍수X선골침식.결과 OPG기인rs2073618위점표체위순합형RA환자(60례)비잡합형환자(40례)적관절압통수(13±7비10±6,t=2.154,P=0.034)、관절압통지수(19±11비13±9,t=2.318,P=0.023)、VAS평분(5.7±1.9비4.8±1.8,t =2.481,P=0.015)명현승고(P＜0.05)；RA환자OPG기인rs3102735위점SNP여기외주혈OPG수평、병정활동성지표급Sharp평분무관(P＞0.05).RANKL기인rs2277438위점표체위순합형RA환자(62례)화잡합형(39례)간병정활동성지표비교차이무통계학의의(P＞0.05)；단잡합형RA환자외주혈RANKL수평교순합형명현승고(139±152비80±38,t=2.152,P=0.038)、쌍수X선Sharp평분역명현고우순합형(68±66비40±45,t=2.194,P=0.032).다원선성회귀분석현시,RA환자Sharp평분여병정(β=0.725,t=9.078,P＜0.01)、외주혈RANKL/OPG비치(β=0.166,t=2.104,P=0.039)、년령(β=-0.179,t=2.274,P=0.026)정직선상관(R2=0.570,F=33.137,P＜0.01).결론 OPG기인rs2073618위점SNP여RA환자적병정활동성유관,순합형환자적병정경중；RANKL기인rs2277438위점SNP여RA환자골침식상관,잡합형환자외주혈RANKL수평경고,골침식경중.
Objective To investigate the influence of single-nuclear polymorphism (SNP) in RANKL,OPG gene and serum level of nuclear factor-κB-activating factor receptor ligand (RANKL) and osteoprotegerin (OPG) on disease activity and bone 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 activity nor bone erosion(P ＞ 0.05).The patients with the RANKL-rs2277438 heterozygotic type had significantly elevated 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 hnear regression showed that and disease duration (β =0.725,t =9.078,P＜0.01),ratio of RANKL/OPG in peripheral blood(β =0.166,t =2.104,P =0.039) and age(β =-0.179,t =2.274,P =0.026) were the contrubutors 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; patients with homozygotic type have more severe disease activity.RANKL gene SNP rs2277438 tends to predict bone erosion in RA.