Interaction Between MiR-125b Expression And Classical Risk Factors In The Risk Of Coronary Heart Disease

Objective:To explore the potential biomarker values of microRNA expression in diagnosing coronary heart disease(CHD)and evaluating the severity of coronary atherosclerosis,and to identify the synergistic effect of microRNA expression with classical risk factors in the risk of coronary heart disease.Methods:From 2012 to 2013,124 consecutive subjects,who underwent coronary angiography for suspected or known coronary atherosclerosis at the Friendship Hospital of Ili Kazakh Autonomous Prefecture in China were enrolled in this study.Blood samples and clinical information were obtained from 66 subjects with CHD and 58 control individuals.A quantitative real-time PCR(qRT-PCR)assay was conducted to confirm the relative expressions of the known CHD-related 20 miRNAs.The severity of coronary atherosclerosis was based on the Gensini scoring system.Crossover analysis was used to calculate odds ratio(OR)and the interaction between microRNA expression and classical risk factors in the risk of coronary heart disease.Results:The expression of miR-125b in plasma of the CHD group was lower than that of the non-CHD group(0.14±0.09?0.18±0.10,p=0.055).As expected,increasing age(p<0.001)and male(p = 0.023)were risk factors for CHD in this population.Additionally,the level of HDL-C(p = 0.020),FBG(p = 0.006),CR(p = 0.033),and Gensini scores(p<0.001)were significantly different between CHD and controls.Moreover,the plasma miR-125b levels significantly decreased following an increasing Gensini score(p=0.037).In addition,Spearman correlation analyses indicated that the Gensini score was negatively associated with miR-125b(r=-0.215,p=0.017).Of all the miRNAs,miR-125b showed the lowest AUC(0.405;95%CI:0.305-0.506,p=0.070)according to Receiver operating characteristic curve(ROC)analysis.We found several synergistic effects between miR-125b and classical risk factors by crossover analysis:age(SI =-50.99,SIM= 5.48,AP = 0.80);gender(SI=1.18,SIM= 0.78,AP= 0.12);CR(SI= 1.46,SIM= 1.00,AP = 0.25);FBG(SI= 1.25,SIM=0.77,AP = 0.16);HDL-C(SI= 1.50,SIM= 0.92,AP= 0.28).Moreover,the proportion of CHD attributable to the interaction of miR-125b and age was as high as 80%.Conclusion:The expression of miR-125b in plasma of the CHD group was lower compared with the controls.Besides,with the increasing of the Gensini score,the expression of miR-125b was significantly decreased.MiR-125b was shown to be a new biomarker in diagnosing CHD and assessing the severity of coronary atherosclerosis.There is also a clear interaction between miR-125b and some classical risk factors in individual's susceptibility to developing CHD,which play an important role in screening out the high risk populations in early stage.