【摘要】 目的 探讨新疆地区绝经后2型糖尿病（T2DM）患者低密度脂蛋白受体相关蛋白6（LRP6）基因位点多态性及突变与骨密度（BMD）的关系，为防治T2DM合并骨质疏松症奠定基础。方法 选取2018年11月至2019年10月石河子大学医学院第一附属医院门诊、住院及社区收治的绝经后女性136例，根据不同血糖及BMD分为糖耐量正常伴骨量正常组（A组，26例）、T2DM伴骨量正常组（B组，27例）、糖耐量正常伴骨量异常组（C组，28例）和T2DM伴骨量异常组（D组，55例）。采用双能X线吸收法测定腰椎（L）_1～4和股骨颈BMD,基质辅助激光解吸电离飞行时间质谱方法测定LRP6基因rs10743980、rs2302685位点基因多态性及频率分布。结果 D组患者中LRP6基因rs10743980位点CC基因型者糖化血红蛋白低于CT/TT基因型，甘油三酯、股骨颈BMD均高于CT/TT基因型；LRP6基因rs2302685位点TT基因型者高密度脂蛋白胆固醇低于TC/CC基因型，甘油三酯、钙、L_1～4 BMD均高于TC/CC基因型。与CC×TT组比较，CT/TT×TT组患者L_1～4 BMD较低，CC×CT/CC组患者股骨颈BMD较低，CT/TT×CT/CC组患者L_1～4、股骨颈BMD降低更明显。高密度脂蛋白胆固醇升高、体重指数降低是股骨颈BMD降低的危险因素，LRP6基因rs10743980位点突变是L_1～4 BMD降低的危险因素（P<0.05）。结论 新疆地区绝经后T2DM患者LRP6基因rs10743980、rs2302685位点多态性与BMD无关，但绝经后T2DM合并骨质疏松症患者中LRP6基因突变参与了BMD的降低。当LRP6基因中两位点同时突变时BMD下降更明显。LRP6基因rs10743980位点突变参与了血糖升高、血脂降低，rs2302685位点突变参与了血脂降低。更多还原

【Abstract】 Objective To investigate the relationship between polymorphism and mutation of low density lipoprotein receptor related protein 6（LRP6） gene locus and bone mineral density（BMD） in postmenopausal women with type 2 diabetes mellitus（T2DM）,so as to lay a foundation for the prevention and treatment of T2DM complicated with osteoporosis（OP）.Methods From November 2018 to October 2019,a total of 136 postmenopausal women were selected from outpatient, inpatient and community treatment in the First Affiliated Hospital of Shihezi University School of Medicine.According to different blood glucose and BMD,they were divided into four groups: normal glucose tolerance（NGT） with normal bone mass（group A,26 cases）,T2DM with normal bone mass（group B,27 cases）,NGT with abnormal bone mass（group C,28 cases） and T2DM with abnormal bone mass（group D,55 cases）.The BMD of lumbar spine 1-4(L_1-4) and femoral neck（FN） were determined by the dual-energy X-ray absorption method.The matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to determine the polymorphism and frequency distribution of rs10743980 and rs2302685 of LRP6 gene.Results In group D,the glycosylated hemoglobin of CC genotype of LRP6 gene rs10743980 was lower than that of CT/TT genotype, triglyceride（TG） and FN BMD were higher than CT/TT genotype.LRP6 rs2302685 locus TT genotype high density liptein cholesterol（HDL-C） was lower than TC/CC genotype, TG, calcium, L_1-4 BMD were higher than TC/CC genotype.Compared with the CC×TT group, the CT/TT×TT group had lower L_1-4 BMD,the CC×CT/CC group had lower FN BMD,the L_1-4 and FN BMD of the CT/TT×CT/CC group decreased more obviously.The increase of HDL-C and the decrease of body mass index were the risk factors for the decrease of FN BMD,and the mutation of LRP6 gene rs10743980 was the risk factor for the decrease of L_1-4 BMD（P<0.05）.Conclusion The polymorphism of LRP6 gene rs10743980 and rs2302685 in postmenopausal women with T2DM in Xinjiang is not related to BMD,but the mutation of LRP6 gene is involved in the decrease of BMD in postmenopausal women with T2DM and OP.When two sites of LRP6 gene mutated at the same time, the decrease of BMD is more obvious.The rs10743980 mutation of LRP6 gene is involved in the increase of blood glucose and the decrease of blood lipid, and the mutation of rs2302685 is involved in the decrease of blood lipid.更多还原