Study On Relationship Between LRP5 Gene Polymorphism And Bone Metabolism In Postmenopausal Women With T2DM In Shihezi

Objective: To study the distribution of LRP5 gen polymorphism of Type 2 diabetes(T2DM)in patients in Shihezi area of Xinjiang in postmenopausal women and to explore the relationship of LRP5 gene polymorphism with bone metabolism and bone mineral density,in order to further seek for pathogenesis of the disease and launch a new thought of diagnosing the population of accurate treatment.Methods: 1.The research population was community and hospitalized postmenopausal women from October 2016 to April 2019,were selected into this study in Shihezi area of Xinjiang.According to the patient’s history,glucose tolerance test and bone mineral density determination results,those people were divided into four groups: normal glucose tolerance(NGT)+ normal bone mass group(A group),the NGT +abnormal bone mass group(B group),T2 DM + normal bone mass(C group)and T2 DM + abnormal bone mass group(D group).2.Measured and recorded the patient’s age,height,weight,menopausal years,waist circumference,hip circumference and other general clinical data.Hemoglobin A 1c(HbAlc)was determined by high pressure liquid chromatography Automatic biochemical analyzer and fasting plasma glucose(FPG),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),Alkaline phosphatase(ALP),plasma calcium(Ca),plasma phosphorus(P),etc was also determined by Roche automatic analyzer.Dual energy X-ray(DEXA)bone mineral density was used to determine lumbar L1-4 and femoral neck BMD.3.Peripheral venous blood was collected,DNA was extracted and gene polymorphism and genotyping of LRP5 genes at rs556442 and rs638051 were detected by time-of-flight mass spectrometry.4.SPSS23.0 statistical software was used for statistical analysis.Results: 1.The baseline age and menopausal years was statistically significant between the groups(P<0.05),and the baseline data were inconsistent.Then covariance analysis was used.2.The influence of age and menopause years on the results was excluded by covariance analysis,and the comparison results between groups: compared with group A,FPG and HbAlc levels of group C and D were higher than that of group A(P<0.01).Compared with group A,levels of L1-4 and femoral neck BMD in group B and group D were lower than those in group A(P<0.01).There was no statistical difference in residual biochemical indexes(P>0.05).3.The genotype distribution of LRP5 gene locus of SNP match to the Hardy-Weinberg genetic balance law(P>0.05).4.The frequency distribution of LRP5 genotypes at the two locus among the groups wasn’t statistically significant(P>0.05).5.To compare the general clinical metabolic index among the several genotypes of LRP5 gene: rs556442 loci: there were statistically significant differences in baseline indicators between genotypes in group A(P<0.05),and differences in baseline data.The comparison of biochemical indicators and BMD was conducted by using cosquare difference compared with that of type AA(wild type),and there was no statistically difference in metabolic indicators of type AG/GG(mutant type)(P>0.05).Comparison of baseline indicators between genotypes in group B(P>0.05),age and menopausal years had statistical differences(P<0.05),baseline data were inconsistent,and covariance analysis was used for comparison of biochemical indicators and BMD.The AG/GG(mutant)femoral neck BMD level was lower than of AA(wild)(P<0.05).There was no significant difference in the remaining metabolic indexes(P>0.05).Comparison of baseline indicators between genotypes in group C(P>0.05)showed that the baseline was homogeneous and comparable.Compared with AA(wild type),AG/GG(mutant type)showed no significant difference in metabolic indexes(P>0.05).Comparison of baseline indicators between genotypes in group D(P>0.05)showed that the baseline was homogeneous and comparable.Comparable with AA(wild type),AG/GG(mutant type)had lower ALP level(P<0.05).Rs638051 loci: comparison of baseline indicators between genotypes in group A(P>0.05).Compared with AA(wild type),AG/GG(mutant type)showed no significant difference in metabolic indexes(P>0.05).Comparison of baseline indicators between genotypes in group B(P>0.05)showed that the baseline washomogeneous and comparable with AA(wild type),AG/GG(mutant type)showed no significant difference in metabolic indexes(P>0.05).Comparison of baseline indicators between genotypes in group C(P>0.05)showed that the baseline was homogeneous and comparable.Compared with AA(wild type),AG/GG(mutant type)showed no significant difference in metabolic indexes(P>0.05).There was a statistical difference in body mass index(BMI)between genotypes in group D(P<0.05),and the baseline data were inconsistent.Therefore,covariance analysis was used for the comparison of biochemical indexes and BMD indexes.Compared with AA(wild type),AG/GG(mutant type)had lower ALP level(P<0.05).There was no significant difference in the remaining metabolic indexes(P>0.05).6.Mμltivariate linear regression analysis of the influencing factors of BMD : taking L1-4(BMD)and femoral neck(BMD)as the dependent variables,and taking age(X1),menopausal years(X2),BMI(X3),WHR(X4),FPG(X5),HbAlc(X6),TG(X7),HDL(X8),LDL(X9),Ca(X10),P(X11),ALP(X12)and genotype(X13)as independent variables,the multivariate linear regression analysis of group D was carried out.In group D,the positive influencing factors of BMD(L1-4)were BMI and TG,while the negative influencing factors were age and menopausal years.The positive influencing factors of BMD(femoral neck)were BMI,and the negative influencing factors were age and menopausal years.Conclusion: 1.LRP5 gene polymorphism at rs556442 and rs638051 has no relationship with abnormal bone metabolism in postmenopausal women in this region,but the mutation of those loci may be related to the disorder of bone metabolism in Shihezi area with postmenopausal T2 DM and abnormal bone mass.2.Among postmenopausal T2 DM women with abnormal bone mass in this region,within limits,high BMI and high TG were positive influencing factors of BMD,while high age and high menopausal years were negative influencing factors of BMD.