新疆绝经后女性2型糖尿病LRP5基因rs3736228、rs3781586位点的基因多态性及突变与糖、脂、骨代谢关系的研究

Study on the relationship in genetic polymorphism and mutation of LRP5 gene rs3736228 and rs3781586 and glucose,lipid and bone metabolism in postmenopausal woman with type 2 diabetes in Xinjiang

目的观察新疆石河子地区绝经后女性2型糖尿病(T2DM)患者糖、脂、骨代谢特征及骨密度(BMD)情况,探讨该人群中低密度脂蛋白受体相关蛋白5(LRP5)基因rs3736228、rs3781586位点的基因多态性及突变与糖、脂、骨代谢指标的关系。方法将新疆石河子地区2016年10月—2017年10月社区、医院门诊及住院绝经后女性按照纳入标准和排除标准选取136例为研究对象,根据患者病史、糖耐量实验及骨密度仪测定骨密度分4组,糖耐量正常与骨量正常组(A组),糖耐量正常与骨量异常组(B组),T2DM与骨量正常组(C组),T2DM与骨量异常组(D组)。测定并记录患者年龄、绝经年限等基线资料,计算体质指数(BMI)等,并检测糖代谢指标(空腹血糖等)、骨代谢指标(血Ca等)、脂代谢指标(甘油三酯等)。采用MALDI-TOF-MS法测定LRP5基因该两个位点基因多态性并进行统计分析。结果①糖代谢指标:与A组比较,C组、D组FPG、HbA1c均高于A组(P<0.01)。脂代谢指标:与A组比较,B组、D组TG低于A组(P<0.05)。骨代谢指标:与A组比较,B组、D组BMD(L1-4)、BMD(股骨颈)低于A组(P<0.01)。②LRP5基因该两个位点SNP基因分型分布符合Hardy-Weinberg遗传平衡定律(P>0.05);同时,该两个位点不同基因型的分布频率和等位基因频率在组间的比较经Pearson Chi-Square检验后发现暂无显著差异(P>0.05)。③LRP5基因rs3736228位点:A组,与CC型(野生型)相比,CT/TT型(突变型)甘油三酯(TG)降低(P<0.05),BMD(L1-4)降低(P<0.05);C组,与CC型(野生型)相比,CT/TT型(突变型)高密度脂蛋白(HDL-C)升高(P<0.01),磷(P)升高(P<0.05);LRP5基因rs3781586位点:B组,与GG型(野生型)相比,GT/TT(突变型)高密度脂蛋白(HDL-C)升高(P<0.05)。结论在新疆石河子地区绝经后女性2型糖尿病人群中,LRP5基因rs3736228、rs3781586位点的基因多态性可能与糖代谢无关,但LRP5基因rs3736228位点的突变可能与脂代谢(TG、HDL-C)、骨代谢(P、BMD)有关,rs3781586位点的突变可能与脂代谢(HDL)有关。

Objective To observe the characteristics of glucose,lipid and bone metabolism and bone mineral density(BMD)in postmenopausal women with type 2 diabetes mellitus(T2DM)in Shihezi district of Xinjiang province,and to investigate the relationship in the polymorphism and mutation of rs3736228 and rs3781586 of LRP5 gene and glucose,lipid and bone metabolism indexes in this population.Methods A total of 136 postmenopausal Han women,who were related in the outpatient department,community,and hospital after hospitalization in Shihezi district of Xinjiang province from October 2016 to October 2017,were selected as the study subjects by the inclusion criteria and exclusion criteria.According to the patient's medicalhistory,glucosetolerance test results and bone mineral density(BMD),they were divided into 4 groups:normal glucose tolerance and normal bone mass(group A),normal glucose tolerance and abnormal bone mass(group B),type 2 diabetes and normal bone mass(group C),and type 2 diabetes mellitus and abnormal bone mass(group D).Baseline data such as patient's age,menopause years were measured and recorded,and body mass index(BMI)was calculated.Simultaneously,glucose metabolism indicators including fasting blood glucose(FBG,etc),bone metabolism indicators(blood Ca,etc),lipid metabolism indicators(triglycerides,etc)were detected.The polymorphisms of rs3736228 and rs3781586 of LRP5 gene were determined by Maldi-Tof-Ms and those data were analyzed statistically.Results①Glucose metabolism index:compared with group A:FPG and HbAlc in group C,group D were all higher than group A(P<0.01).Lipid metabolism index:compared with group A,TG in group B and group D was lower than that in group A(P<0.05).Bone metabolism index:compared with group A,BMD(L1-4)and BMD(femoral neck)in group B and group D were lower than those in group A(P<0.01).②The distribution of SNP genotypes at rs3736228,rs3781586 of LRP5 conformsed to the Hardy-Weinberg genetic equilibrium law(P>0.05).The distribution frequency and allele frequency of LRP5 genotypes rs3736228,rs3781586 were compared among the groups.Pearson chi-square test showed no significant difference(P>0.05).③Rs 3736228 locus of LRP5 gene:in group A,compared with CC(wild type),CT/TT(mutated type)triglyceride(TG)decreased(P<0.05),BMD(L1-4)decreased(P<0.05).In group C,compared with CC(wild type),CT/TT(mutated type)high-density lipoprotein(HDL-C)increased(P<0.05),phosphorus increased(P<0.05).Rs 3781586 locus of LRP5 gene:in group B,compared with GG(wild type),GT/TT(mutated type)high-density lipoprotein(HDL-C)increased(P<0.05).Conclusion In the Xinjiang Shihezi district among postmenopausal women with type 2 diabetes,rs3736228,rs3781586 loci of LRP5 gene polymorphism may be irrelevant to glucose metabolism,but the mutation of rs3736228 of LRP5 gene locus may be related to lipid metabolism and bone metabolism(TG,HDL-C,BMD,P),and the mutation of rs3781586 may be related to lipid metabolism(HDL-C).