摘要
目的探讨SOST基因和低密度脂蛋白5(low density lipoprotein 5,LRP5)基因多态性及突变与石河子地区绝经后2型糖尿病(type 2 diabetes mellitus,T2DM)女性骨代谢的关系,为绝经后T2DM伴骨质疏松(osteoporosis,OP)的发生给予指导。方法选取2018年7月至2019年7月期间在新疆石河子大学医学院第一附属医院内分泌代谢科门诊就诊的135例绝经后女性作为研究对象(45岁≤年龄<87岁),按照骨密度(bone mineral density,BMD)结果分为骨量正常组(n=52)和骨量异常组(n=83),再依据是否伴T2DM分为4个亚组,血糖正常伴骨量正常组(n=26)、血糖正常伴骨量异常组(n=28)、T2DM伴骨量正常组(n=26)及T2DM伴骨量异常组(n=55);记录其年龄等一般基线资料;生化分析仪(全自动性)检测碱性磷酸酶(alkaline phosphatase,ALP)、三酰甘油(triacylglycerol,TG)与空腹血糖(fasting plasma glucose,FPG)等生物化学指标参数;双能X线吸收检测法(dual-energy X-ray absorptiometry,DXA)法检测BMD;飞行时间质谱(time-of-flight mass spectrometry,TOF-MS)法检测LRP5基因与SOST基因位点的多态性。结果在LRP5基因rs901825位点中,与A组相比,D组基因型分布差异有统计学意义(P<0.01);在LRP5基因rs7125942位点中,与A组相比,B组基因型分布差异有统计学意义(P<0.05)。在D组中,SOST基因rs10534024位点,TCC.DEL/TCC.TCC基因型(突变型)的BMD(股骨颈)低于DEL.DEL基因型(野生型)(0.69±0.13 vs 0.76±0.10,P<0.05);LRP5基因rs7125942位点,在TG上,CC基因型(野生型)、CG基因型(突变型)分别为4.12±0.79、3.22±1.04,前者显著偏高(P<0.01)。在B组分析SOST基因rs851054位点发现,在TG上,相较AG/AA基因型(突变型),GG基因型(野生型)显著偏高(2.11±1.19 vs 1.30±0.80,P<0.05)。交互作用:SOST基因rs851054位点与LRP5基因rs7125942位点的交互作用对BMD(股骨颈)产生影响(P<0.05);SOST基因和LRP5基因4个位点的交互作用对BMD(股骨颈)产生影响(P<0.01)。多元线性回归分析:SOST基因rs10534024位点、体质量指数、TG与于BMD(L1-4)水平正向相关;LRP5基因rs7125942位点、绝经年限(BMD股骨颈)水平与负向相关。结论通过调查石河子区域绝经后女性发现,其LRP5基因rs901825位点基因多态性和骨代谢、糖代谢可能相关;在LRP5基因rs7125942位点,基因多态性与骨代谢有关且是BMD降低的危险因素,基因突变可能与脂代谢有关。对石河子区域绝经后女性调查发现,其SOST基因rs10534024位点的基因突变和BMD可能相关。SOST基因和LRP5基因的交互作用可能是BMD(股骨颈)降低的危险因素。
Objective To explore the relationship between SOST gene and low density lipoprotein 5(LRP5)gene polymorphisms and mutations and bone metabolism in postmenopausal T2DM women in Shihezi area,and to provide reference for the occurrence of postmenopausal T2DM with osteoporosis(OP).Methods The subjects were divided into two groups:normal bone mass group and abnormal bone mass group.Then based on whether they were with type 2 diabetes mellitus(T2DM),the patients were divided into four sub groups:normal glucose with bone mass group,normal glucose with abnormal bone mass group,T2DM group with normal bone mass group,and T2DM with abnormal bone mass group.Calcium(Ca),fasting plasma glucose(FPG),triacylglycerol(TG),alkaline phosphatase(ALP)etc.clinical biochemical data were determined by Automatic biochemical analyzer;dual-energy X-ray absorptiometry(DXA)method to detect bone mineral density(BMD);and the polymorphisms of the LRP5 and SOST gene were detected by time-of-flight mass spectrometry(TOF-MS).Results(1)The rs901825 polymorphism of the LRP5 genotype distribution was statistically significant(P<0.05)in group D compared with group A.The rs7125942 polymorphism of the LRP5 genotype distribution was statistically significant(P<0.05)in group B compared with group A.(2)In group D,at the SOST rs10534024 site,BMD of TCC.DEL/TCC.TCC genotype(mutant)was lower than that of DEL.DEL genotype(wild-type)(0.69±0.13 vs 0.76±0.10,P<0.05);LRP5 gene rs7125942 locus,on TG,CC genotype(wild type)and CG genotype(mutant type)were 4.12±0.79 and 3.22±1.04,respectively,the former was significantly higher(P<0.01);In group B,at the SOST rs851054 site,TG of GG genotype(wild-type)was higher than that of AG/AA genotype(Mutant)(2.11±1.19 vs 1.30±0.80,P<0.05).(3)Interaction analysis showed that the interaction between rs851054 of SOST gene and rs7125942 of LRP5 gene affected BMD(femoral neck)(P<0.05).The interaction between SOST gene and LRP5 gene has an effect on BMD(femoral neck)(P<0.01).Multiple linear regression analysis found rs10534024 of SOST gene,TG and body mass index were positively correlated with BMD(L1-4).Rs7125942 of LRP5 gene and menopause duration were negatively correlated with BMD(femoral neck).Conclusion The polymorphism and frequency distribution of LRP5 gene rs901825 and rs7125942 in postmenopausal women in Shihezi may be related to bone metabolism;The genetic mutation of rs7125942 locus of LRP5 gene may be related to lipid metabolism of postmenopausal women.The mutation of rs10534024 of SOST gene may be related to BMD in postmenopausal women in Shihezi.The interaction between SOST gene and LRP5 gene is a risk factor for BMD(femoral neck)reduction.
作者
宋丽敏
李思源
李军
赵会荣
李佳佳
王双
Song Limin;Li Siyuan;Li Jun;Zhao Huirong;Li Jiajia;Wang Shuang(Department of Endocrinology and Metabolism,the First Affiliated Hospital of College of Medicine,Shihezi University,Shihezi 832000,Xinjiang Autonomous Region, China;Department of Histology and Embryology, College of Medicine,Shihezi University,Shihezi 832000,Xinjiang Autonomous Region, China;Department of Endocrinology and Metabolism,the Second People's Hospital of Nanyang, Nanyang 473012,Henan Province, China;Department of Endocrinology and Metabolism,Shanghai Yangpu Central Hospital,Shanghai 200090, China)
出处
《首都医科大学学报》
CAS
北大核心
2022年第2期269-274,共6页
Journal of Capital Medical University
基金
新疆兵团区域创新引导计划(2018BB040)
石河子大学成果转化与技术推广项目(CGZH201911)
社会发展领域兵团科技攻关计划项目(2021AB031)。
