绝经后2型糖尿病患者护骨因子基因rs4355801、rs6993813位点多态性及突变与骨代谢的关系  

Correlations of polymorphisms and mutations of osteoprotegerin gene rs4355801 and rs6993813 loci with bone metabolism in postmenopausal women with type 2 diabetes mellitus

作　　者：王丽珍 李军[1] 李思源[2] 向清淋 任艳霞 王娅宁 WANG Lizhen;LI Jun;LI Siyuan;XIANG Qinglin;REN Yanxia;WANG Yaning(Department of Endocrinology and Metabolism,The First Affiliated Hospital of Shihezi University,Shihezi 832000,Xinjiang Uygur Autonomous Region,China;Department of Histology and Embryology,Shihezi University School of Medicine,Shihezi 832000,Xinjiang Uygur Autonomous Region,China;Department of Critical Care Medicine,Dazhou Central Hospital,Dazhou 635000,Sichuan,China)

机构地区：[1]石河子大学第一附属医院内分泌代谢科,石河子832000 [2]石河子大学医学院组织学与胚胎学教研室,石河子832000 [3]达州市中心医院重症医学科,达州635000

出　　处：《海军军医大学学报》2024年第2期189-197,共9页Academic Journal of Naval Medical University

基　　金：2018年度兵团科技发展专项(2018BB040);石河子大学成果转化与技术推广项目(CGZH201911)。

摘　　要：目的探讨绝经后2型糖尿病患者护骨因子(OPG)基因rs4355801、rs6993813位点多态性及突变与骨代谢的关系。方法选取2020年10月至2021年10月就诊于石河子大学第一附属医院的绝经后女性200例,根据病情分为糖耐量及骨量正常组(A组,52例)、糖耐量正常但骨量异常组(B组,43例)、骨量正常的2型糖尿病组(C组,47例)、2型糖尿病合并骨量异常组(D组,58例)。收集患者年龄、身高、体重、绝经年限等基线资料,计算BMI、腰臀比。用罗氏全自动生化分析仪测定甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血钙、血磷、碱性磷酸酶(ALP)、空腹血糖(FPG)等生物化学指标,HPLC测量糖化血红蛋白(HbA1c),双能X线测量L1~4椎体及股骨颈骨密度,飞行时间质谱测定OPG基因rs4355801、rs6993813位点多态性及基因型分型。采用多元线性回归分析筛选骨密度的影响因素。使用SHEsis软件进行单核苷酸多态性位点的连锁不平衡分析及单体型分析。结果4组间年龄、BMI、腰臀比存在差异(P<0.05)。与A组、B组相比,C组、D组的FPG、HbA1c水平均升高(均P<0.05);与B组相比,C组HDL-C水平升高、ALP水平降低(均P<0.05);与C组相比,D组ALP水平升高(P<0.05);与A组、C组相比,B组、D组的L_(1~4)椎体骨密度及股骨颈骨密度水平均降低(均P<0.05)。OPG基因rs4355801、rs6993813位点均符合Hardy-Weinberg平衡。rs4355801位点基因型及等位基因频率分布组间差异均无统计学意义(均P>0.05);与A组相比,C组、D组rs6993813位点基因型分布均存在差异(均P<0.05),而等位基因频率分布在各组间差异均无统计学意义(均P>0.05)。C组rs4355801位点突变型患者FPG、HbA1c水平均低于野生型患者(均P<0.05),D组rs4355801位点突变型患者L_(1~4)椎体骨密度水平高于野生型患者(P<0.05),D组rs6993813位点突变型患者血磷水平低于野生型患者、股骨颈骨密度水平高于野生型患者(均Objective To investigate the correlations of polymorphisms and mutations of osteoprotegerin(OPG)gene rs4355801 and rs6993813 loci with bone metabolism in postmenopausal women with type 2 diabetes mellitus(T2DM).Methods From Oct.2020 to Oct.2021,200 postmenopausal women who visited The First Affiliated Hospital of Shihezi University were enrolled and divided into normal glucose tolerance and bone mass group(group A,n=52),normal glucose tolerance but abnormal bone mass group(group B,n=43),T2DM with normal bone mass group(group C,n=47),and T2DM with abnormal bone mass group(group D,n=58).The baseline data such as age,height,weight,and years since menopause(YSM)were collected,and body mass index(BMI)and waist-hip ratio(WHR)were calculated.Biochemical indicators such as triglyceride(TG),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),blood calcium,blood phosphorus,alkaline phosphatase(ALP),and fasting blood glucose(FBG)were measured by Roche automatic biochemical analyzer.Glycosylated hemoglobin(HbA1c)was measured by high-performance liquid chromatography.Bone mineral densities(BMDs)of the lumbar spine(L_(1-4))and neck of femur(NOF)were measured by dual energy X-rays.Polymorphism and genotyping of OPG gene rs4355801 and rs6993813 loci were determined by time-of-flight mass spectrometry.Multiple linear regression analysis was used to analyze the influencing factors of BMD.Linkage disequilibrium analysis and haplotype analysis of single nucleotide polymorphism loci were performed using SHEsis software.Results There were significant differences in age,BMI,and WHR among the 4 groups(P<0.05).Compared with groups A and B,the levels of FPG and HbA1c in groups C and D were significantly increased(all P<0.05).Compared with group B,the level of HDL-C in group C was significantly increased,while the level of ALP was significantly decreased(P<0.05).Compared with group C,the level of ALP in group D was significantly increased(P<0.05).The BMD(L_(1-4))and BMD(NOF)in groups B and D were signific

关 键 词：绝经后女性 2型糖尿病 护骨因子 骨质疏松症 基因多态性 基因突变 

分 类 号：R580[医药卫生—内分泌] R587.1[医药卫生—内科学]