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| 新疆绝经后2型糖尿病女性SOST蛋白表达及基因 rs851056、rs1230399位点多态性与骨代谢关系的研究 |
| A study on the relationship between SOST protein expression and the gene polymorphisms of rs851056 and rsl230399 in the SOST gene and bone metabolism in postmenopausal women with type 2 diabetes mellitus in Xinjiang |
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| DOI：10.3969/j.issn.1006-7108.2021.07.014 |
| 中文关键词: SOST基因多态性 基因突变 2型糖尿病 骨质疏松症 骨密度 SOST蛋白 |
| 英文关键词:SOST Gene polymorphism gene mutation type 2 diabetes mellitus osteoporosis bone mineral density SOST protein |
| 基金项目:新疆生产建设兵团区域创新引导计划（201SBB040);石河子大学成果转化与技术推广项目（CGZH201911) |
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| 中文摘要: |
| 目的 检测新疆石河子地区绝经后2型糖尿病（type 2 diabetes mellitus，T2DM)女性血清硬化蛋白（sclerostin，SOST蛋 白）表达水平，探讨SOST蛋白表达及基因rs851056、rsl230399位点基因多态性与骨代谢的关系，筛选骨质疏松症 (osteoporosis，OP)早期诊断和治疗的潜在候选基因位点，为OP患者的临床个体化治疗提供理论依据。方法 共纳人136例研究对象，根据OGTT及骨量分为A( -/-)、B( +/-)、C(-/+)、D( +/+)4组。收集各组的一般资料并计算体质量指数（body mass index，BMI)、腰臀比。通过罗氏生化仪检测受试者FPG、HbAlc、TG、Ca、P等糖、骨、脂代谢指标；运用双能X线法测定受试者腰椎（L1~4)及股骨颈骨密度（bone mineral density，BMD)；运用ELISA法测定SOST蛋白表达水平；通过Mass ARRAY质谱仪测定rs851056、rsl230399位点基因多态性。运用协方差分析比较各组间生化指标及BMD差异、χ2检验分析比较两个位点各基因型和基因频率、相关分析SOST蛋白与骨密度相关性，多元线性回归分析BMD影响因素。结果 ①B组、D组与A 组相比，SOST基因rs851056位点基因型和等位基因频率比较差异有统计学意义（P<0. 01)；rs1230399位点基因型和等位基因频率比较差异无统计学意义（P >0. 05) ；②rs851056位点不同基因型相比，C组中GG型HDL、Ca、ALP均低于GC/CC型（P <0.05），D组中GG型BMD(L1~4)髙于GC/CC型（P<0.05)；③与A组相比，C组、D组SOST蛋白表达水平升髙；④SOST蛋白水平与BMD(L1~4)呈负相关；⑤rs851056位点突变、BMI及TG降低是BMD(L1~4)降低的危险因素。BMI降低、ALP及绝经年限增加是BMD(股骨颈）降低的危险因素。结论 ①新疆绝经后T2DM女性中，SOST基因rs851056位点基因多态性及基因频率分布可能与骨、糖代谢异常有关。该位点的基因突变可能与BMD的下降及脂代谢有关；②SOST蛋白表达水平与骨密度有关，是BMD降低的危险因素；③绝经后T2DM女性，低BMI、低TG、髙ALP以及绝经年限长是BMD降低的危险因素。 |
| 英文摘要: |
| Objective To detect the expression level of SOST protein in postmenopausal women with T2DM in Shihezi，Xinjiang，thereby exploring the relationship between SOST expression，as well as the genetic polymorphism in the rs851056 and rs1230399 gene， and bone metabolism. Therefore， we can screen potential candidate gene loci for early diagnosis and treatment of osteoporosis (OP), and to provide theoretical basis for clinical individualized treatment of OP patients. Methods A total of 136 subjects were included; according to OGTT and bone mass, they were divided into four groups： A ( -/-)，B (+/-)，C ( -/+)， D (+/+). We collected general data of everyone and then calculated BMI and waist-to-hip ratio. Roche biochemical analyzer was used to measure the FPG，HbA1c，TG，Ca，P and other indicators for sugar，bone，and lipid metabolism. Dual-energy X-ray enzyme-linked immunosorbent assay was used to determine the expression level of SOST protein. ARRAY mass spectrometer was used to detect genetic polymorphisms in rs851056 and rs1230399 gene. Covariance analysis was used to compare the differences in biochemical indicators and BMD among the groups，meanwhile the χ2 test analysis was used to compare the genotypes and gene frequencies of the two loci. Correlation analysis was used to correlate SOST protein with bone density. In addition，the factors affecting BMD were analyzed by multiple linear regression method . Results ① In the comparison among group B and D with group A，the genotype and allele frequency of rs851056 locus in SOST gene showed significantly difference (P <0. 01) ；whereas the genotype and allele frequency at rs1230399 locus showed no difference (P >0.05).② Compared with different genotypes of rs851056，HDL，Ca and ALP of GG genotype in group C were lower than those of GC/CC type (P<0. 05) ； and BMD (L1-4) of GG genotype in group D was higher than that of GC/CC type (P<0. 05).③ Compared with group A，the expression level of SOST proteinin C and D groups increased.④ SOST protein level was negatively correlated with BMD (L1-4).⑤ Rs851056 mutation， BMI and TG decrease represented risk factors for BMD (L1-4) reduction; decreased BMI，ALP and increased menopausal period represented risk factors for decreased BMD ( femoral neck). Conclusion ① The rs851056 polymorphism and frequency distribution of SOST gene in postmenopausal T2DM women in Xinjiang may be associated with abnormal bone and glucose metabolism. The mutation may be related to the decrease of BMD and lipid metabolism;② The expression level of SOST protein is related to bone mineral density，which is a risk factor for the decrease of BMD;③ In postmenopausal women with T2DM，low BMI，low TG，high ALP and long menopausal years are risk factors for the decrease of BMD. |
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