长链非编码RNA NR002578 NR038264和NR046252在原发性痛风患者外周血单个核细胞的表达及其临床意义

Expression of long non-coding RNA NR_002578,NR_038264 and NR_046252 in peripheral blood mononuclear cells of patients with primary gout and its clinical significance

目的探讨可靶向miR-223的3个长链非编码RNA(lncRNA)NR002578、NR038264和NR046252在原发性痛风性关节炎(GA)入组患者PBMCs中的表达及可能的临床意义。方法收集满足研究条件痛风患者60例[包括急性期痛风(AG)30例和间歇期痛风(IG)30例]和50名健康体检者(健康对照组)周围静脉血标本、临床资料及实验室指标;用实时荧光定量PCR(RT-qPCR)方法检测3个lncRNAs在GA与健康对照组PBMCs表达水平,比较3个lncRNAs表达量在不同组别的差异并与临床指标间做相关性分析,构建受试者工作特征曲线(ROC)评估lncRNAs在痛风诊断中的可能潜能。计量资料符合正态分布使用t检验或方差分析,非正态分布用Mann-WhitneyU检验或Kruskal-WallisH检验,3组间比较采用SNK。结果①NR002578在GA组的表达低于健康对照组[60.2(16.8,100.1)×10^(-3)与149.5(92.6,221.8)×10^(-3);Z=-5.75,P<0.001],亚组分析发现其在AG组低于IG和健康对照组[34.3(8.6,72.8)×10^(-3)与88.3(47.7,109.6)×10^(-3)与149.5(92.6,221.8)×10^(-3),H=40.12,P<0.001],且在IG组低于健康对照组(P<0.001);NR046252在GA组的表达则高于健康对照组[6.5(2.1,21.5)×10^(-3)与2.1(1.2,3.5)×10^(-3);Z=-4.21,P<0.001],AG与IG组均高于健康对照组[6.3(2.0,12.0)×10^(-3)与7.2(2.4,30.6)×10^(-3)与2.1(1.2,3.5)×10^(-3);H=21.33,P<0.001],但AG与IG之间差异无统计学意义(P>0.05)。②Spearman相关性分析发现痛风患者中NR002578的表达量与ESR(r=-0.29,P=0.024)、hsCRP(r=-0.35,P=0.006)呈负相关。③NR002578和NR046252用于诊断痛风ROC曲线下面积分别为0.819和0.750。结论NR002578和NR046252在痛风患者的异常表达提示其可能参与痛风发病。

Objective To explore the three long non-coding RNA(long non-coding ribonucleic acid,the expression of lncRNA NR_002578,NR_038264 and NR_046252)in peripheral blood mononuclear cells(PBMCs)of patients with primary gout arthritis(GA)and their clinical value.Methods Peripheral venous blood,clinical data and laboratory data were collected from 60 gout patients(including 30 AG patients in acute stage and 30 IG patients in intermittent stage)and 50 healthy subjects(HC group).Quantitative reverse transcription PCR(RT-qPCR)was used to detect the expression levels of PBMCs of 3 lncRNAs in GA and HC groups,and the differences of 3 lncRNAs expression levels in different groups were compared and the correlation analysis was conducted with clinical indicators.Receiver operating characteristic curve(ROC)was constructed to evaluate the possible efficacy of lncRNAs in gout diagnosis.The measurement data conforming to normal distribution were tested by t test or variance analysis,and non-normal distribution were tested by Mann-Whitney U test or Kruskal-Wallis H test.The comparison among the three groups was conducted by SNK.Results①The expression of NR_002578 in GA was significantly lower than that in HC[60.2(16.8,100.1)×10^(-3)vs 149.5(92.6,221.8)×10^(-3),Z=-5.75,P<0.001],subgroup analysis showed that the expression of NR_002578 in AG was significantly lower than that in IG and HC[34.3(8.6,72.8)×10^(-3)vs 88.3(47.7,109.6)×10^(-3)vs 149.5(92.6,221.8)×10^(-3),H=40.12,P<0.001],and lower in IG than that in HC(P<0.001).The expression of NR_046252 in GA was significantly higher than that in HC[6.5(2.1,21.5)×10^(-3)vs 2.1(1.2,3.5)×10^(-3),Z=-4.21,P<0.001].The expression of NR_046252 in AG and IG were higher than that of the HC group[6.3(2.0,12.0)×10^(-3)vs 7.2(2.4,30.6)×10^(-3)vs 2.1(1.2,3.5)×10^(-3),H=21.33,P<0.001],but there was no significant difference between the AG and IG group(P>0.05).②Spearman correlation analysis showed that NR_002578 expression was negatively correlated with erythrocyte sedimentation rate(ESR)(r=-0.29,P=0.024)and hypersensitive C-reactive protein(hs-CRP)(r=-0.35,P=0.006)in gout patients.③The areas under ROC curve of NR_002578 and NR_046252 for diagnosing gout were 0.819 and 0.750,respectively.Conclusion The abnormal expression of NR_002578 and NR_046252 in gout patients suggests that NR_002578 may be involved in the pathogenesis of gout.