中华风湿病学杂志
中華風濕病學雜誌
중화풍습병학잡지
CHINESE JOURNAL OF RHEUMATOLOGY
2012年
11期
732-737
,共6页
裴必伟%徐胜前%刘童%邓娟%沈晓濛%潘发明%徐建华
裴必偉%徐勝前%劉童%鄧娟%瀋曉濛%潘髮明%徐建華
배필위%서성전%류동%산연%침효몽%반발명%서건화
关节炎,类风湿%多态性,单核苷酸%骨密度%RANKL基因%OPG基因%疾病活动性
關節炎,類風濕%多態性,單覈苷痠%骨密度%RANKL基因%OPG基因%疾病活動性
관절염,류풍습%다태성,단핵감산%골밀도%RANKL기인%OPG기인%질병활동성
Arthritis,rheumatoid%Polymorphism,single nucleotide%Bone density%Receptor activator for nuclear factor-κB ligand gene%Osteoprotegerin gene%Disease activity
目的 探讨骨保护素基因(TNFRSF11B) 1181G＞C(rs2073618)、163A＞G(rs3102735)位点和核因子κB活化因子受体配体(RANKL)基因(TNFRSF 11)401A＞G (rs2277438)位点单核苷酸多态性(SNP)对类风湿关节炎(RA)疾病易感性及其骨密度和疾病活动性的影响.方法 采用连接酶检测反应(LDR)聚合酶链反应(PCR)方法检测200例RA患者和201名健康对照组骨保护素基因rs2073618、rs3102735位点和RANKL基因rs2277438位点SNP；采用双能X线骨密度仪(DEXA)法测定其股骨和腰椎部位骨密度.比较其等位基因分布频率、基因型频率及单倍体型在2组中的分布,并比较不同基因型RA患者骨密度及疾病活动性的差别.统计学方法采用方差分析,t检验和x2检验.结果 ①骨保护素基因rs2073618位点、rs3102735位点和RANKL基因rs2277438位点各等位基因及基因型分布频率在RA组与对照组中差异均无统计学意义(P＞0.05).3个位点单倍体型研究表明:骨保护素和RANKL基因单倍体型(rs2073618G-rs2277438G-rs3102735G)携带者RA疾病易感性明显降低(1.5％与6.0％,OR:0.216,95％CI:0.081～0.575,P=0.0008),骨保护素和RANKL基因单倍体型(rs2073618G-rs2277438A-rs31 02735G)携带者RA易感性明显增加(14.5％与8.4％,OR:1.862,95％CI:1.179～2.943,P=0.007).②RANKL基因rs2277438位点表达为纯合型(AA和GG型)的RA患者(62例)腰椎3(1.05±0.22与0.93±0.26,t=2.314,P=0.023)、腰椎4(1.06±0.24与0.94±0.28,t=2.207,P=0.030)、腰椎2～4(1.04±0.21与0.89±0.28,t=2.788,P=0.007)部位骨密度均明显高于杂合型(AG型)RA患者(39例)；骨保护素基因rs2073618和rs3102735位点不同基因型RA患者间骨密度差异无统计学意义(P＞0.05).③骨保护素基因rs2073618位点表达为纯合型(CC、GG型)的RA患者(60例)在以下疾病活动性指标上明显高于表达为杂合型(CG型)的RA患者(40例):压痛关节数(13±7与10±6,t=2.154,P=0.034)、压痛关节指数(19±11与13±9,t=2.318,P=0.023)、疼痛视觉模拟(VAS)评分(5.7±1.9与4.8±1.8,t=2.481,P=0.015).RANKL基因rs2277438位点、骨保护素基因rs3102735位点不同基因型RA患者间各疾病活动性指标差异无统计学意义(P＞0.05).结论 骨保护素基因rs2073618、rs3102735位点和RANKL基因rs2277438位点SNP与中国籍汉族RA患者易感性无关,但骨保护素和RANKL基因单倍体型(rs2073618G-rs2277438G-rs3102735G)为RA的保护性因素,而单倍体型(rs 2073618G-rs2277438A-rs31 02735G)是危险因素.RANKL基因rs2277438位点SNP与RA骨代谢相关；骨保护素基因rs2073618位点SNP与RA患者疾病活动性相关.
目的 探討骨保護素基因(TNFRSF11B) 1181G＞C(rs2073618)、163A＞G(rs3102735)位點和覈因子κB活化因子受體配體(RANKL)基因(TNFRSF 11)401A＞G (rs2277438)位點單覈苷痠多態性(SNP)對類風濕關節炎(RA)疾病易感性及其骨密度和疾病活動性的影響.方法 採用連接酶檢測反應(LDR)聚閤酶鏈反應(PCR)方法檢測200例RA患者和201名健康對照組骨保護素基因rs2073618、rs3102735位點和RANKL基因rs2277438位點SNP；採用雙能X線骨密度儀(DEXA)法測定其股骨和腰椎部位骨密度.比較其等位基因分佈頻率、基因型頻率及單倍體型在2組中的分佈,併比較不同基因型RA患者骨密度及疾病活動性的差彆.統計學方法採用方差分析,t檢驗和x2檢驗.結果 ①骨保護素基因rs2073618位點、rs3102735位點和RANKL基因rs2277438位點各等位基因及基因型分佈頻率在RA組與對照組中差異均無統計學意義(P＞0.05).3箇位點單倍體型研究錶明:骨保護素和RANKL基因單倍體型(rs2073618G-rs2277438G-rs3102735G)攜帶者RA疾病易感性明顯降低(1.5％與6.0％,OR:0.216,95％CI:0.081～0.575,P=0.0008),骨保護素和RANKL基因單倍體型(rs2073618G-rs2277438A-rs31 02735G)攜帶者RA易感性明顯增加(14.5％與8.4％,OR:1.862,95％CI:1.179～2.943,P=0.007).②RANKL基因rs2277438位點錶達為純閤型(AA和GG型)的RA患者(62例)腰椎3(1.05±0.22與0.93±0.26,t=2.314,P=0.023)、腰椎4(1.06±0.24與0.94±0.28,t=2.207,P=0.030)、腰椎2～4(1.04±0.21與0.89±0.28,t=2.788,P=0.007)部位骨密度均明顯高于雜閤型(AG型)RA患者(39例)；骨保護素基因rs2073618和rs3102735位點不同基因型RA患者間骨密度差異無統計學意義(P＞0.05).③骨保護素基因rs2073618位點錶達為純閤型(CC、GG型)的RA患者(60例)在以下疾病活動性指標上明顯高于錶達為雜閤型(CG型)的RA患者(40例):壓痛關節數(13±7與10±6,t=2.154,P=0.034)、壓痛關節指數(19±11與13±9,t=2.318,P=0.023)、疼痛視覺模擬(VAS)評分(5.7±1.9與4.8±1.8,t=2.481,P=0.015).RANKL基因rs2277438位點、骨保護素基因rs3102735位點不同基因型RA患者間各疾病活動性指標差異無統計學意義(P＞0.05).結論 骨保護素基因rs2073618、rs3102735位點和RANKL基因rs2277438位點SNP與中國籍漢族RA患者易感性無關,但骨保護素和RANKL基因單倍體型(rs2073618G-rs2277438G-rs3102735G)為RA的保護性因素,而單倍體型(rs 2073618G-rs2277438A-rs31 02735G)是危險因素.RANKL基因rs2277438位點SNP與RA骨代謝相關；骨保護素基因rs2073618位點SNP與RA患者疾病活動性相關.
목적 탐토골보호소기인(TNFRSF11B) 1181G＞C(rs2073618)、163A＞G(rs3102735)위점화핵인자κB활화인자수체배체(RANKL)기인(TNFRSF 11)401A＞G (rs2277438)위점단핵감산다태성(SNP)대류풍습관절염(RA)질병역감성급기골밀도화질병활동성적영향.방법 채용련접매검측반응(LDR)취합매련반응(PCR)방법검측200례RA환자화201명건강대조조골보호소기인rs2073618、rs3102735위점화RANKL기인rs2277438위점SNP；채용쌍능X선골밀도의(DEXA)법측정기고골화요추부위골밀도.비교기등위기인분포빈솔、기인형빈솔급단배체형재2조중적분포,병비교불동기인형RA환자골밀도급질병활동성적차별.통계학방법채용방차분석,t검험화x2검험.결과 ①골보호소기인rs2073618위점、rs3102735위점화RANKL기인rs2277438위점각등위기인급기인형분포빈솔재RA조여대조조중차이균무통계학의의(P＞0.05).3개위점단배체형연구표명:골보호소화RANKL기인단배체형(rs2073618G-rs2277438G-rs3102735G)휴대자RA질병역감성명현강저(1.5％여6.0％,OR:0.216,95％CI:0.081～0.575,P=0.0008),골보호소화RANKL기인단배체형(rs2073618G-rs2277438A-rs31 02735G)휴대자RA역감성명현증가(14.5％여8.4％,OR:1.862,95％CI:1.179～2.943,P=0.007).②RANKL기인rs2277438위점표체위순합형(AA화GG형)적RA환자(62례)요추3(1.05±0.22여0.93±0.26,t=2.314,P=0.023)、요추4(1.06±0.24여0.94±0.28,t=2.207,P=0.030)、요추2～4(1.04±0.21여0.89±0.28,t=2.788,P=0.007)부위골밀도균명현고우잡합형(AG형)RA환자(39례)；골보호소기인rs2073618화rs3102735위점불동기인형RA환자간골밀도차이무통계학의의(P＞0.05).③골보호소기인rs2073618위점표체위순합형(CC、GG형)적RA환자(60례)재이하질병활동성지표상명현고우표체위잡합형(CG형)적RA환자(40례):압통관절수(13±7여10±6,t=2.154,P=0.034)、압통관절지수(19±11여13±9,t=2.318,P=0.023)、동통시각모의(VAS)평분(5.7±1.9여4.8±1.8,t=2.481,P=0.015).RANKL기인rs2277438위점、골보호소기인rs3102735위점불동기인형RA환자간각질병활동성지표차이무통계학의의(P＞0.05).결론 골보호소기인rs2073618、rs3102735위점화RANKL기인rs2277438위점SNP여중국적한족RA환자역감성무관,단골보호소화RANKL기인단배체형(rs2073618G-rs2277438G-rs3102735G)위RA적보호성인소,이단배체형(rs 2073618G-rs2277438A-rs31 02735G)시위험인소.RANKL기인rs2277438위점SNP여RA골대사상관；골보호소기인rs2073618위점SNP여RA환자질병활동성상관.
Objective To investigate the relationship between single-nucleotide polymorphism (SNP)in receptor activator for nuclear factor-κB ligand (RANKL),osteoprotegerin (OPG) gene and rheumatoid arthritis (RA).Methods In our study,3 SNPs in the genes of OPG (2 SNP:rs2073618,rs3102735) and RANKL (1 SNP:rs2277438) by ligase detection reactions from 200 RA and 201 controls were examined.BMD values of different areas were assessed using dual-energy X-ray absorptiometry.Clinical and laboratory parameters were collected.Analysis of variance,t-test and x2 test were used for statistical analysis.Results No signi-ficant differences in the distribution of the alleles and genotypes were observed between case group and the control group (P＞0.05).The haplotype analysis for RANKL and OPG SNPs showed that the rs2073618/rs2277438/rs3102735 GGG haplotype could reduce the risk of RA (1.5％ vs 6.0％,P=0.008; OR 0.216;95％CI:0.081 to 0.575) and the GAG haplotype increased the risk of RA (14.5％ vs 8.4％,P=0.007; OR 1.862,95％CI:1.179 to 2.943).Patients with RANKL-rs2277438 AA or GG genotypes (n=6) had significantly higher BMD values compared to those with AG genotypes (n=39) at spine lumber 3 (1.05±0.22 vs 0.93±0.26,t=2.314,P=0.023),spine lumber 4 (1.06±0.24 vs 0.94±0.28,t=2.27,P=0.030),spine lumber 2-4 (1.04±0.21 vs 0.89±0.28,t=2.788,P=0.007).The tender joint counts (13±7 vs 10±6),tender joint index (19±11 vs 13±9),and VAS score (5.7±1.9 vs 4.8±1.8) differed significantly between patients with the OPG-rs2073618 CC or GG genotypes (n=60) and GC genotypes (n=40).Conclusion The rs2073618/rs2277438/rs3102735GGG haplotype may be protective against RA,while GAG haplotype may increase the susceptibility to RA.RANKL gene SNP rs2277438 may affect BMD value at spine lumber,and OPG gene SNP rs2073618 may influence the disease activity of RA patients.
