Relationship Between OPG Gene Rs4355801,rs6993813 Polymorphism And Bone Metabolism In Postmenopausal Women With T2DM

Object: 1.To study the expression of OPG gene rs4355801 and rs6993813 polymorphisms in postmenopausal women with type 2 diabetes mellitus(T2DM)in Shihezi,Xinjiang.2.To explore the relationship between OPG gene polymorphism,gene mutation and bone metabolism,bone mineral density(BMD)in postmenopausal women with type 2 diabetes mellitus in Shihezi,Xinjiang,and reveal the pathogenesis of type 2 diabetes mellitus complicated with osteoporosis from the genetic level,so as to provide new ideas and prevention basis for the precise treatment of this population.Methods: 1.Postmenopausal women were selected as the research objects from October 2018 to October 2019 in Shihezi,Xinjiang.According to the inclusion criteria and exclusion criteria(n = 200),medical history,glucose tolerance test and BMD measurements,they were divided into four groups: normal glucose tolerance(NGT)and bone mass(52 cases in group A),normal glucose tolerance and abnormal bone mass(43 cases in group B),T2 DM and normal bone mass(47 cases in Group C),and T2 DM and abnormal bone mass(58 cases in Group D).2.Determine and record the general clinical indicators of the selected subjects:(1)general materials: age,menopause years,calculate the body mass index(BMI)and waist hip ratio(WHR);(2)indicators of glucose,adipose and bone mentalism;1)glycometabolic index: glycosylated hemoglobin(Hb Alc),fasting plasma glucose(FPG)and so on;2)lipid metabolism index: low density lipoprotein cholesterol(LDL-C),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)etc.3)bone metabolism index: alkaline phosphatase(ALP),serum calcium,serum phosphorus and so on;Hb Alc was determined by high pressure liquid chromatography(HPLC),and other metabolic indexes were determined by Roche biochemical analyzer.(4)bone density: the BMD of L1-4 and neck of femur(NOF)were measured by dual energy X-ray(DEXA).3.The polymorphism and genotyping of rs4355801 and rs6993813 of OPG gene were determined by MALDI-TOF-MS.4.Spss26.0 software was used for statistical analysis.Results: 1.Comparison of general data among the four groups,the menopausal years of group B and D(15.74±9.67,20.10±9.58)were increased compared with group A(11.48±9.42),and the age of group D(69.03±9.74)was increased compared with group A(58.44±9.24)(all P <0.05).2.Analysis of covariance was used to balance the effects of age and menopausal years.Comparison of results among groups: the expression levels of FPG and Hb A1 c in group C(9.10±2.44;8.42±1.95)and group D(8.57±2.56;8.19±1.87)were higher than those in group A(5.00±0.59;6.01±0.83)(all P <0.05);the expression levels of HDL-C in group C(1.93±1.06)were higher than those in group A(1.43±0.49)(all P <0.05).Bone metabolism and BMD: the expression levels of L1-4 and femoral neck BMD in group B(0.93±0.12;0.78±0.13),group D(0.95±0.10;0.77±0.10)were lower than those in group A(1.16±0.20;1.02±0.25)(P<0.05).There was no significant difference among other indicators.3.The genotyping and allele frequencies of rs4355801 and rs6993813 of 0pg gene were in accordance with Hardy Weinberg equilibrium(P >0.05).There was no significant difference in genotype and allele frequency among group B,C,D and group A(P >0.05).4.Comparison of different genotypes of OPG gene: rs4355801: in group A and B,there were no significant differences in baseline data and metabolic indexes between mutant(GG+GA)and wild type(AA)(all P >0.05);in group C,the expression levels of FPG and Hb A1 c in mutant(GG+GA)were significantly lower(8.33±1.90;7.70±1.83)Compared with the wild type(AA)(9.78±2.68;9.05±1.86),the differences were statistically significant(all P <0.05).In group D,the BMD(L1-4)level of mutant(GG+GA)(1.16±0.23)was higher than that of wild type(AA)(0.98±0.12),the differences were statistically significant(P <0.05).rs6993813: in group A,B and C,there was no significant difference in baseline data and metabolic indexes between the mutant(CC+TC)and the wild type(TT)(all P >0.05);In group D,the P level of mutant type(CC+TC)was lower than that of wild type(TT)(1.05±0.13vs1.13±0.16,P <0.05);The BMD(NOF)level of mutant type(CC+TC)was higher than that of wild type(TT)(0.80±0.09vs0.74±0.12,P <0.05).5.Multiple linear regression analysis of the influencing factors of BMD: at rs4355801 and rs6993813 loci,the increase of menopausal years was the influencing factor of the decrease of BMD(L1-4)and BMD(NOF),and the decrease of triglyceride was the influencing factor of the decrease of BMD(L1-4).In rs4355801 locus,the decrease of HDL-C was the impression factor of the decrease of BMD(NOF).In rs6993813 locus,the gene polymorphism and the decrease of P were the influencing factors of the decrease of BMD(NOF).Conclusions: 1.OPG gene rs6993813 locus gene polymorphism and rs4355801,rs6993813 locus gene mutations are involved in the occurrence and development of T2 DM complicated with OP in postmenopausal women in Shihezi area.2.The mutation at rs4355801 site of OPG gene may be involved in the abnormal regulation of glucose metabolism in this population.From the point of view of gene locus polymorphism and mutation,it provides a basis for the explanation of disease mechanism,disease prevention and treatment.