| Objective:.1.To observe the expression of LRP5 protein and the gene polymorphisms at rs599083,rs7125942,rs901825 in post-menopausal women in Shihezi of Xinjiang under different glucose and bone metabolism lever.2.To explore the correlation between LRP5 protein expression and gene polymorphisms and BMD and bone metabolism indexes,and provide a basis for the prevention and treatment of T2 DM with OP in Shihezi of Xinjiang.Methods: 1.Collect postmenopausal women who came to our hospital from June 2018 to June 2019.According to OGTT and history of diabetes,BMD,the selected objects are divided into four groups :normal glucose tolerance combined and normal bone mass(NGT,group A,50 cases),normal glucose tolerance and abnormal bone mass(group B,53case),abnormal glucose tolerance and normal bone mass(group C,57case),abnormal glucose tolerance and abnormal bone mass(group D,87case).2.Measurement of general clinical indicators of subjects:measure the age,menopausal years,height,weight,waist circumference,hip circumference,and calculate Body Mass Index(BMI)and Waist Hip Ratio,WHR);Measurement of biochemical indicators: Roche automatic biochemical analyzer was used to measure fasting blood glucose(FPG),total cholesterol(TC),triglyceride(TG),blood Ca,blood P,etc.Bone ineral density(BMD)was determined by dual-energy X-ray absorptiometry.3.Sequenom time-of-flight mass spectrometry was used to determine the genotypes of the LRP5 rs599083,rs901825,and rs7125942 loci.4.Enzyme-linked immunosorbent assay(ELISA)was used to determine the LRP5 protein lever.5.Statistical analysis: Calculate the genotype frequency and allele frequency of the LRP5 rs599083,rs901825,and rs7125942 loci.5.SPSS20.0 was used for statistical analysis,and the measurement data was mean ±standard deviation,Chi-square testt was used to compare the three-locus genotypes and allele distribution frequencies.The correlation between LRP5 protein and clinical indicators by correlation analysis;The influencing factors of BMD by multiple linear regression analysis.Results: 1.Comparison of baseline data between groups: The age and the age of menopause in group B and group D were increased than group A,(P<0.05).2.After analysis of covariance,the comparison of biochemical indicators between the groups :the FPG and Hb A1c% in group C and group D were higher than group A(8.25±2.91,8.00±2.40vs5.00±0.63;7.61 ±1.45,7.76±1.56vs5.8±0.44),(P<0.01).TG in group B was lower than group A(1.31±0.79vs2.00±1.43),(P<0.05).The expression levels of BMD(L1-4)and BMD(femoral neck)in group B and D are lower than group A(0.89±0.16,0.92±0.10vs1.17±0.16;0.72±0.11,0.76±0.11vs0.94±0.13),(P<0.01).3.LRP5 protein expression analysis: The concentration of LRP5 protein in groups B,C,and D than group A was reduced(9.767± 6.231,11.340±6.637,8.877±4.09 vs 19.281±11.922),(P<0.05).LRP5 protein concentration was negatively correlated with age(r=-0.322,P= 0.001),menopausal years(r=-0.267,P= 0.008),FPG(r =-0.225,P= 0.025);LRP5 protein concentration was positively correlated with BMI(r = 0.226,P=0.024),BMD(L1-4)(r = 0.284,P= 0.004),BMD(femoral neck)(r = 0.297,P=0.003).4.Analysis of LRP5 genotypes and allele frequencies: The LRP5rs599083,rs901825,and rs7125942 loci genes were tested to meet the Hardy-Weinberg equilibrium(P>0.05).The three genotypes is TT(54%),GT(39%),and GG(7%)of rs599083 loci.The T allele frequency is57%,and the G allele frequency is 43%.LRP5 gene rs901825 loci has three genotypes GG(43%),GC(49%),CC(7%).G allele distribution frequency is 68%,C allele is 32%,The frequency of genotype in group D was statistically significant than group A(P<0.01).LRP5 gene rs7125942 loci has two genotypes CC(90%)and GC(10%),the G allele distribution frequency was 91%,and the C frequency was 9%.Compared to group A,the frequency of genotype in group C was statistically significant than group A(P<0.01).5.Comparison of different indicators of Mutant Genotypes and Wild Genotypes in LRP5 loci: rs599083 loci:in group A,P,BMD(L1-4)of mutant genotypes(GG /GT)was decreased than wild genotypes(TT)(1.08±0.11 vs 1.17±0.15,1.11±0.13 vs 1.23±0.17),(P<0.05);in group C,the age,LDL and BMD(L1-4)of Genotypes(GG/GT)was reduced(58.33±8.68 vs 63.36±9.13,2.42±1.01 vs 2.83±0.86,1.14±0.15vs1.23±0.19)than Wild Genotypes(TT),(P<0.05).Rs901825 loci: in group A,age of mutant menotypes of menotypes(GC/CC)was higher(65.06±9.88 vs 55.91±8.73)and BMD(femoral neck)was lower(0.89±0.11 vs 1.01±0.10)than wild genotypes(GG),(P<0.05);in group B,LDL of menotypes(GC/CC)was higher than wild genotypes(GG)(2.98±0.86 vs 1.99± 0.70),(P <0.01);in group C,age、age of menopausein、LDL and ALP of GC/CC was higher than wild genotypes(GG),(65.19±8.26vs54.24±6.92,15.93±7.84vs6.48±5.97,3.27±1.05 vs 2.40±0.94,75.19±21.51 vs 62.67± 11.49);group D,FPG,Hb A1c%,HDL of menotypes genotype(GC/CC)was lower than wild genotypes(GG)(7.52±1.98 vs 9.36 ± 2.86,7.36±1.24±1.98 vs 8.74±2.17,1.21±0.31 vs1.45±0.05),(P<0.05).Rs7125942: in group A,LDL of menotypes genotype(GC)was lower than wild genotypes(CC)(2.24±0.40 vs 2.87±0.90),(P<0.05);in group C,BMD(L1-4)of menotypes genotype(GC)was lower than wild genotypes(CC)(1.03±0.17vs1.21±0.18),(P<0.05).6.Multiple linear regression analysis: rs599083 gene polymorphism,high age and high ALP were BMD(L1-4)negative influence factors,high LRP5 protein concentration was BMD(L1-4)positive influence factor;high age was BMD(femoral neck)negative influence factor,higher LRP5 protein concentration and within limits high BMI were BMD(femoral neck)positive influence factors.Conclusions: LRP5 gene rs599083,rs901825,7125942 gene polymorphisms,mutations reduced LRP5 protein expression and caused abnormal bone metabolism,thus affecting the occurrence and development of T2 DM with OP women in Shihezi,Xinjiang. |
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