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
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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。
Objective:MATN3encodes extracellular matrix proteins, and might modulate chondrocyte differentiation. The aim of this study is to explore if MATN3polymorphisms influence bone mineral density (BMD), fracture, vertebral fracture, bone turnover and25(OH)VitD in postmenopausal women.
Methods:1488postmenopausal women of Han nationality were randomly selected in Beijing. Fracture and vertebral fracture phenotypes were accertained by questionnaire and vertebral X-ray reading. BMD of lumber spine (L2-4), femoral neck (FN) and total hip were measured by dual energy X-ray absorptiometry (DXA). An automated Roche electrochemiluminescence system was used to test serum bone turnover and25(OH)VitD. Four tagging single nucleotide polymorphisms (tagSNPs) in MATN3were determined by TaqMan Pre-Designed SNP Genotyping Assays in Real-Time PCR System. We used multiple statistic methods to test the associations between SNP genotypes, haplotypes and osteoporosis phenotypes. We also analyzed correlations among bone turnover,25(OH)VitD, age, BMD, fracture and vertebral fracture.
Results:
1. Polymorphisms of rs1109663and rs6734005were significantly associated with total hip BMD (p=0.000-0.032and0.005-0.026, respectively), and the significance persisted even after correction to-multiple testing. The minor allele of rs6734005had protective effects for total hip BMD. The association of rs10178256and total hip BMD was also suggestive (p=0.009-0.037).Consistent with these results, haplotype GAC was significantly associated with total hip BMD (p=0.005-0.023), and p value remained significant after correction to multiple testing. GAC also exerted protective influence against hip osteoporosis.
2. MATN3polymorphisms were not associated with β-CTX, P1NP or25(OH)VitD.3. The serum concentration of β-CTX and P1NP declined with aging and then rose up in postmenopausal women, and they were negatively correlated with BMD of lumber spine, FN and total hip. Serum25(OH)VitD level of postmenopausal women in Beijing was remarkably low (13.10±5.37ng/ml), and decreased with aging. We did not find correlation between bone turnover,25(OH)VitD and fracture or vertebral fracture.
Conclusion:This study suggested for the first time that MATN3polymorphisms might influence total hip BMD variation in postmenopausal women, and it was not related to bone turnover or25(OH)VitD.
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。
Objective:MATN3encodes extracellular matrix proteins, and might modulate chondrocyte differentiation. The aim of this study is to explore if MATN3polymorphisms influence bone mineral density (BMD), fracture, vertebral fracture, bone turnover and25(OH)VitD in postmenopausal women.
Methods:1488postmenopausal women of Han nationality were randomly selected in Beijing. Fracture and vertebral fracture phenotypes were accertained by questionnaire and vertebral X-ray reading. BMD of lumber spine (L2-4), femoral neck (FN) and total hip were measured by dual energy X-ray absorptiometry (DXA). An automated Roche electrochemiluminescence system was used to test serum bone turnover and25(OH)VitD. Four tagging single nucleotide polymorphisms (tagSNPs) in MATN3were determined by TaqMan Pre-Designed SNP Genotyping Assays in Real-Time PCR System. We used multiple statistic methods to test the associations between SNP genotypes, haplotypes and osteoporosis phenotypes. We also analyzed correlations among bone turnover,25(OH)VitD, age, BMD, fracture and vertebral fracture.
Results:
1. Polymorphisms of rs1109663and rs6734005were significantly associated with total hip BMD (p=0.000-0.032and0.005-0.026, respectively), and the significance persisted even after correction to-multiple testing. The minor allele of rs6734005had protective effects for total hip BMD. The association of rs10178256and total hip BMD was also suggestive (p=0.009-0.037).Consistent with these results, haplotype GAC was significantly associated with total hip BMD (p=0.005-0.023), and p value remained significant after correction to multiple testing. GAC also exerted protective influence against hip osteoporosis.
2. MATN3polymorphisms were not associated with β-CTX, P1NP or25(OH)VitD.3. The serum concentration of β-CTX and P1NP declined with aging and then rose up in postmenopausal women, and they were negatively correlated with BMD of lumber spine, FN and total hip. Serum25(OH)VitD level of postmenopausal women in Beijing was remarkably low (13.10±5.37ng/ml), and decreased with aging. We did not find correlation between bone turnover,25(OH)VitD and fracture or vertebral fracture.
Conclusion:This study suggested for the first time that MATN3polymorphisms might influence total hip BMD variation in postmenopausal women, and it was not related to bone turnover or25(OH)VitD.
引文
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