首页|DKK1基因启动子甲基化水平与糖尿病微血管病变合并骨质疏松的相关性研究

DKK1基因启动子甲基化水平与糖尿病微血管病变合并骨质疏松的相关性研究

Correlation between DKK1 promoter methylation level and diabetic microangiopathopathy complicated with osteoporosis

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目的 探讨Dickkopf相关蛋白1(Dickkopf 1,DKK1)基因启动子甲基化水平与2型糖尿病(type 2 diabetes,T2DM)微血管病变合并骨质疏松(osteoporosis,OP)的相关性.方法 收集2019年1月至2022年12月于临沂市中心医院就诊的T2DM微血管病变患者作为研究对象,根据是否合并OP症将患者分为观察组(44例)和对照组(58例).测量研究对象的腰椎(L1~4)骨密度,检测骨代谢指标,包括血钙、血磷、25-维生素 D3[25-hydroxy vitamin D3,25-(OH)D3]、甲状旁腺素(parathyroid hormone,PTH)、Ⅰ型胶原C-末端肽(C-terminal telopeptide of typeⅠ collagen,CTX)、Ⅰ型前胶原 N-末端肽(procollagen of aminoterminal propeptide,PINP)及抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRACP)水平;测定DKK1基因启动子甲基化水平.结果 观察组的DKK1基因启动子甲基化水平为5.17%±0.73%,显著高于对照组的3.81%±0.61%,差异有统计学意义(t=5.22,P<0.001).观察组的25-(OH)D3水平、PTH和腰椎骨密度显著低于对照组,CTX和TRACP水平显著高于对照组(t=5.58、4.35、4.12、4.05、4.17,P均<0.001).在所有患者中,DKK1基因启动子甲基化水平与CTX、TRACP呈显著正相关关系(r=0.41、0.39,P=0.006、0.027),与PTH、腰椎骨密度呈显著负相关关系(r=-0.38、-0.43,P=0.015、0.003).ROC曲线分析结果显示,DKK1基因甲基化水平区分T2DM微血管病变合并和未合并OP的曲线下面积为0.841(0.762~0.921),灵敏度和特异度分别为86.4%、72.4%.结论 DKK1基因启动子甲基化水平与T2DM微血管病变患者发生OP及骨代谢指标有关.
Objective To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1(DKK1)gene and diabetic microangiopaopathy complicated with osteoporosis.Methods Pa-tients with type 2 diabetes mellitus(T2DM)microangiopathopathy who were admitted to our hospital from Jan.2019 to Dec.2022 were collected as research objects,and divided into observation group(44 cases)and control group(58 cases)according to whether they were complicated with osteoporosis.Bone mineral density(BMD)of lumbar spine(L1-4)was measured,and bone metabolism indexes,including serum calcium,serum phosphorus,25-hydroxy vitamin D3[25-hydroxy vitamin D3,25-(OH)D3],PTH,C-terminal telopeptide of typeⅠ collagen(CTX),procollagen of aminoterminal propeptide(PINP)and tartrate resistant acid phosphatase(TRACP)levels were detected;The promoter methylation level of DKK1 gene was determined.Results The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%,which was significantly higher than that in the control group(3.81%±0.61%),with statistical significance(t=5.22,P<0.001).The 25-(OH)D3 level,PTH and lumbar bone density in the observation group were significantly lower than those in the control group,while the CTX and TRACP levels were significantly higher than those in the control group(t was 5.58,4.35,4.12,4.05 and 4.17,respectively,P<0.001).In all patients,the promoter methylation level of DKK1 gene was significantly posi-tively correlated with CTX and TRACP(r was 0.41 and 0.39,P was 0.006 and 0.027,respectively),and signifi-cantly negatively correlated with PTH and lumbar bone density(r was-0.38 and-0.43,respectively).P=0.015 and 0.003,respectively).ROC curve analysis showed that the area under the curve of DKK1 methylation level to distin-guish type 2 diabetes microangionopathy with and without osteoporosis was 0.841(0.762-0.921),and the sensitivity and specificity were 86.4%and 72.4%,respectively.Conclusion The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

DKK1 geneDNA methylationType 2 diabetes mellitusMicroangiopathyOsteoporosis

黄建国、王晓辉、王江杰、刘甲、冯磊、孙立霞、李富元

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临沂市中心医院血管外科,临沂 276400

临沂市中心医院手足外科,临沂 276400

临沂市中心医院内分泌科,临沂 276400

Dickkopf相关蛋白1基因 DNA甲基化 2型糖尿病 微血管病变 骨质疏松

山东省自然科学基金

ZR2020QH080

2024

中华内分泌外科杂志
中华医学会

中华内分泌外科杂志

CSTPCD
影响因子:0.657
ISSN:1674-6090
年,卷(期):2024.18(1)
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