北京地区汉族绝经后妇女MATN3基因多态性与骨质疏松表型的关联研究

发布时间：2018-07-23 16:36

【摘要】：目的：MATN3基因编码胞外基质蛋白,并可能对软骨分化过程起调控作用。本研究的目的是探讨MATN3基因多态性与绝经后妇女骨密度、骨折、椎体骨折、骨转换标志物和25(OH)VitD的关系。方法：在北京地区随机抽样收集1488名汉族绝经后妇女作为研究对象,通过问卷调查及胸腰椎X线片阅读分别确定骨折及椎体骨折表型。以双能X线吸收仪检测腰椎(L2-4)、股骨颈和全髋的骨密度,以罗氏自动检测仪采用电化学发光免疫测定法检测血清β-CTX、P1NP和25(OH)VitD水平。使用TaqMan基因分型技术检测MATN3基因4个标签SNP的多态性。采用logistic回归等统计学方法分析SNP位点基因型和单体型与各骨质疏松表型的关系,以相关分析等方法分析骨转换标志物和25(OH)VitD与年龄、骨密度、骨折和椎体骨折的关系。结果： 1. MATN3基因rs11096633位点和rs6734005位点的多态性与全髋骨密度显著相关(P值分别为0.000-0.032和0.005-0.026),并且这种显著性经过对多重检验的校正后仍然存在。其中rs6734005位点的少见等位基因A对髋部骨密度起保护作用。rs10178256位点与全髋骨密度的相关性也具有提示意义(p=0.009-0.037)。单体型6AC与全髋骨密度显著相关(p=0.005-0.023),对髋部骨密度起保护作用,其显著性经过对多重检验校正后仍有统计学意义。 2. MATN3基因多态性与β-CTX、P1NP和25(OH)VitD水平无关。 3.绝经后妇女β-CTX和P1NP水平随年龄增长呈现先下降后上升的趋势,并与腰椎、股骨颈和全髋的骨密度呈显著负相关。北京地区绝经后妇女的血清25(OH)VitD水平明显偏低(13.10±5.37ng/ml),25(OH)VitD水平随着年龄的增长而逐渐下降。本研究未发现β-CTX、P1NP和25(OH)VitD与骨折、椎体骨折存在相关性。结论：本研究首次揭示MATN3基因多态性可能影响绝经后妇女全髋骨密度的变异,而与骨转换标志物和维生素D水平没有相关性。
[Abstract]:Objective to encode extracellular matrix protein (ECM) and regulate cartilage differentiation. The aim of this study was to investigate the association of MATN3 gene polymorphism with bone mineral density, fracture, vertebral fracture, bone turnover marker and 25 (OH) VitD in postmenopausal women. Methods: 1488 postmenopausal women of Han nationality were randomly sampled in Beijing area. The phenotypes of fracture and vertebral body fracture were determined by questionnaire survey and X-ray reading of thoracolumbar vertebrae. Bone mineral density (BMD) of lumbar spine (L2-4), femoral neck and total hip were measured by dual energy X-ray absorptiometry. Serum 尾 -CTXT P1NP and 25 (OH) VitD levels were measured by electrochemiluminescence immunoassay with Roche automatic detector. TaqMan genotyping technique was used to detect the polymorphism of SNP tagged MATN3 gene. The relationship between the genotype and haplotype of SNP locus and the phenotypes of osteoporosis was analyzed by logistic regression, and the relationship between bone turnover markers and 25 (OH) VitD with age, bone density, fracture and vertebral fracture was analyzed by correlation analysis. Results: 1. The polymorphism of rs11096633 locus and rs6734005 locus of MATN3 gene was significantly associated with total hip bone density (P = 0.000-0.032 and 0.005-0.026, respectively). The rare allele A of rs6734005 locus has protective effect on hip bone density. The correlation between rs10178256 locus and total hip bone density is also significant (p 0.009-0.037). Haplotype 6AC was significantly correlated with total hip bone density (p0. 005-0. 023) and had a protective effect on hip bone density. The polymorphism of MATN3 gene was not associated with the levels of 尾 -CTXG P1NP and 25 (OH) VitD. The levels of 尾 -CTX and P1NP in postmenopausal women decreased first and then increased with age, and were negatively correlated with bone mineral density of lumbar vertebrae, femoral neck and total hip. The serum 25 (OH) VitD level of postmenopausal women in Beijing was significantly lower than that of postmenopausal women (13.10 卤5.37ng/ml). There was no correlation between 尾-CTX P1NP and 25 (OH) VitD and vertebral fracture. Conclusion: MATN3 gene polymorphism may affect the variation of total hip bone density in postmenopausal women for the first time, but has no correlation with bone turnover markers and vitamin D levels.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R580;R3416

【参考文献】