The Relationship Between OPG Protein,OPG,RANK Gene Polymorphisms And Bone Metabolism In Postmenopausal Women With T2DM

Objective:Explore the osteoprotegerin（OPG）protein expression,OPG gene rs11573819,rs3134069 locus,nuclear factorκB receptor activator of nuclear factorκB（RANK）gene rs884205,rs8083511polymorphisms and mutations.The relationship between polymorphism and mutation and bone metabolism provides a basis for the prevention and treatment of type 2 diabetes（T2DM）and osteoporosis（OP）.Methods:1.Include postmenopausal women in our hospital’s outpatient department,inpatient department and surrounding communities as research subjects.According to the results of oral glucose tolerance test（OGTT）,previous diabetes history and dual energy X-ray absorptionmetry（DEXA）test results.The subjects were divided into four groups:normal glucose tolerance（NGT）combined with normal bone mass（NBM）group（group A）,T2DM combined with NBM group（group B）,NGT combined with abnormal bone mass（Abnormal bone mass,ABM）group（C group）,T2DM combined with ABM group（D group）.2.Measure and record the general information of the subject:age,menopause years（MD）,height（H）,weight（W）,etc.,and calculate the participant’s body mass index（BMI）and Waist Hip Ratio（WHR）;Roche automatic analyzer detects glucose,lipid,and bone metabolism indicators;high pressure liquid method for determination of glycosylated hemoglobin（Hb A1c）.DEXA measures BMD(L_1-4,FN).3.Use Enzyme-Linked Immunosorbent Assay（ELISA）to determine the OPG protein concentration.4.To determine the polymorphism and mutation of OPG and RANK gene locus by time-of-flight mass spectrometry.5.Use SPSS 22.0 statistical analysis.Results:1.Compared with group A,group B and group D have FPG（9.22±2.21,4.93±0.57;8.48±2.71,4.93±0.57）and Hb A1c（8.65±1.74,5.29±1.15;8.09±1.79,5.29±1.15）The level is higher;the HDL-C（2.02±1.11,1.41±0.47）level of group B is higher;the BMD(L_1-4)of group C and D（0.96±0.10,1.15±0.22;0.95±0.09,1.15±0.22）And BMD（FN）（0.78±0.09,1.02±0.11;0.76±0.11,1.02±0.11）level is lower.2.Compared with group A,OPG protein expression concentration in groups B and D increased[191.43（181.75,199.95）,175.81（152.46,178.39）;181.07（177.16,200.45）,175.81（152.46,178.39）],C Group decreased[122.09（105.60,135.99）,175.81（152.46,178.39）];Compared with group B,the OPG protein expression concentration of group D decreased[181.07（177.16,200.45）,191.43（181.75,199.95）].OPG protein level and age（r=0.340,P=0.001）,years of menopause（r=0.249,P=0.008）,FPG（r=0.356,P=0.000）,Hb A1c（r=0.222,P=0.014）,BMD(L_1-4)（r=0.219,P=0.004）,BMD（FN）（r=0.307,P=0.003）are positively correlated.3.The OPG and RANK genes are in line with the Hardy-Weinberg balance after testing.Compared with group A,RANK gene rs884205 locus,CC,CA,AA genotype and C,A allele distribution frequency of C group are different.4.OPG gene:（1）Rs11573819 locus:Compared with GG type,the level of AG+AA type FPG（9.69±3.38,8.12±1.95）in group B is higher.（2）Rs3134069 locus:Compared with type AA,the level of AC+CC type FPG（10.70±2.07,8.67±2.37）in group B is higher;group C AC+CC type BMD(L_1-4,FN)（0.84±0.09,0.97）±0.11;0.69±0.12,0.80±0.12)lower level;D group AC+CC type Ca（2.16±0.22,2.32±0.14）,HDL-C[1.22（1.02,1.51）,1.35（1.17,1.93）]The level is low.5.RANK gene:（1）Rs884205 locus:Compared with CC type,CA+AA type age[72.00（61.50,77.00）,65.00（51.50,71.25）]is higher in group C;BMD（FN）（0.70±0.13,0.81）±0.12)The level is low.（2）Rs8083511 locus:Compared with AA type,the level of AC+CC type WHR[0.93（0.91,0.96）,0.88（0.83,0.94）]in group B is higher,and the level of HDL-C（2.09±1.15,1.49±0.59）is higher.Low;D group AC+CC type MD[23.00（15.75,27.25）,17.50（2.00,24.75）],P（1.30±0.15,1.06±0.15）level is higher;Ca（1.75±0.16,2.27±0.21）level Lower.6.Multiple linear regression analysis:As age increases,the level of HDL-C decreases,and the decrease of OPG concentration is a risk factor for the decrease of BMD(L_1-4);the level of HDL-C decreases,the level of LDL-C increases,the BMI decreases,and the level of P increases.RANK gene rs884205 polymorphism is a risk factor for BMD（FN）reduction.Conclusion:1.Among postmenopausal T2DM women in Shihezi,Xinjiang,OPG gene mutations lead to down-regulation of OPG protein expression and RANK gene polymorphisms and mutations,which participate in the occurrence and development of OP in this population.2.OPG gene mutation is involved in the abnormal regulation of glucose and lipid metabolism;RANK gene mutation is involved in the abnormal regulation of lipid metabolism in this population.