新疆绝经后2型糖尿病女性DKK1基因rs1896367、rs2241529位点的基因多态性及突变与骨代谢的关系

Gene Polymorphisms and Mutations of rs1896367 and rs2241529 of Dickkopf-Associated Protein 1 Gene in Post-menopausal Women with Type 2 Diabetes Mellitus and Their Relationship with Bone Metabolism in Xinjiang

摘要: 目的：探讨新疆地区绝经后2型糖尿病(T2DM)女性DKK1基因rs1896367、rs2241529位点的基因多态性及突变与骨代谢指标的关系。方法：选取新疆地区绝经后T2DM女性136例，根据病史，糖耐量试验(OGTT)及双能X线(BMD)分为4组：A组(糖耐量正常伴骨量正常组26例)，B组(糖耐量正常伴骨量异常组28例)，C组(T2DM伴骨量正常组27例)，D组(T2DM伴骨量异常组55例)。测定并记录空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三脂(TG)、钙(Ca)、磷(P)等临床生化指标；Sequenom飞行时间质谱法测定DKK1基因rs1896367、rs2241529位点的基因多态性；双能X线吸收法(dual energy X-ray, DEXA)测定腰椎(L1-4)、股骨颈的骨密度(bone mineral density, BMD)。结果：1) DKK1基因rs1896367位点：与A组相比，B组、C组、D组的基因型及等位基因的频率分布有统计学差异(P < 0.05)；DKK1基因rs2241529位点：与A组相比，C组、D组的基因型及等位基因的频率分布有统计学差异(P < 0.05)；2) LDL-C测定：DKK1基因rs1896367、rs2241529位点突变型(AG + AA; AG + GG) (3.389 ± 1.038; 3.445 ± 1.045)低于野生型(GG; AA) (4.835 ± 0.035; 4.835 ± 0.035)，(P < 0.05)；3) 多元线性回归结果：绝经年限、甘油三脂是BMD (L1-4)及BMD (股骨颈)影响因素(P < 0.05)。结论：1) 在新疆绝经后T2DM女性中，DKK1基因rs1896367、rs2241529位点的基因多态性与糖、骨代谢有关。2) 多元线性回归方程结果显示：绝经年限增高、及甘油三脂的降低是BMD降低的危险因素。

Abstract: Objective: To investigate the relationship between polymorphism and mutation of rs1896367 and rs2241529 of DKK1 gene and bone metabolism in postmenopausal women with type 2 diabetes mellitus (T2DM) in Xinjiang. Methods: A total of 136 postmenopausal women with T2DM in Xinjiang were selected and divided into 4 groups according to their medical history, glucose tolerance test (OGTT) and BMD. Group A (26 patients with normal glucose tolerance and normal bone mass), group B (28 patients with normal glucose tolerance and abnormal bone mass), group C (27 patients with normal bone mass and T2DM), and group D (55 patients with T2DM and abnormal bone mass). Fasting blood glucose (FPG), glycated hemoglobin (HbA1c), triglyceride (TG), calcium (Ca), phos-phorus (P) and other clinical biochemical indexes were measured and recorded. The polymor-phisms of rs1896367 and rs2241529 of DKK1 gene were determined by Sequenom time-of-flight mass spectrometry. Bone mineral density (BMD) of lumbar spine (L1-4) and femoral neck was measured by dual energy X-ray (DEXA). Results: 1) rs1896367 locus of DKK1 gene: Compared with group A, the frequency distribution of genotype and allele in groups B, C and D had statistical dif-ferences (P < 0.05). rs2241529 locus of DKK1 gene: Compared with group A, the frequency distri-bution of genotypes and alleles in groups C and D had statistical differences (P < 0.05). 2) LDL-C de-termination: rs1896367 and rs2241529 mutations of DKK1 gene (AG+AA; AG+GG) (3.389 ± 1.038; 3.445 ± 1.045) lower than wild type (GG; AA) (4.835 ± 0.035; 4.835 ± 0.035), (P < 0.05); 3) Multiple linear regression results: Menopause years and triglycerides were the influencing factors of BMD (L1-4) and BMD (neck of femur) (P < 0.05). Conclusion: 1) In postmenopausal T2DM women in Xin-jiang, the polymorphisms of rs1896367 and rs2241529 of DKK1 gene are related to glucose and bone metabolism. 2) The results of multiple linear regression equation showed that increasing menopause years and decreasing triglycerides were risk factors for decreasing BMD.