An Sp1 Binding Site Polymorphism in the COLIA1 Gene Predicts Osteoporotic Fractures in Both Men and Women
An Sp1 Binding Site Polymorphism in the COLIA1 Gene Predicts Osteoporotic Fractures in Both Men and Women
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DOI：
10.1359/jbmr.1998.13.9.1384
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发表时间：
1998-09
影响因子：
6.2
通讯作者：
B. Langdahl;S. Ralston;S. Grant;E. Eriksen
中科院分区：
文献类型：
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作者：
B. Langdahl;S. Ralston;S. Grant;E. Eriksen
遗传因素在骨质疏松症的发病机制中起着重要作用，最近的研究表明，I型胶原蛋白α1（COLIA 1）基因中的多态性Sp1结合位点与英国女性的骨量和椎骨骨折相关。然而，关于COLIA 1 Sp1多态性在其他人群中的预测价值的信息是有限的，并且还没有在男性乳腺癌患者中进行研究。有鉴于此，我们在丹麦男性和女性的病例对照研究中分析了COLIA 1基因型与骨密度和骨转换生化标志物的关系以及骨质疏松性骨折的存在。通过聚合酶链反应分析从外周血样本中提取的基因组DNA，确定COLIA 1基因型，并与骨量、骨转换生化标志物以及375例骨质疏松性椎体骨折患者和正常对照的骨折存在相关。当分别分析对照组（n = 195）和骨折组（n = 180）的数据时，COLIA 1基因型对骨量或生化指标无显著影响。然而，与年龄匹配的对照组相比，骨折病例的基因型分布有显著差异。（χ2 = 16.48，n = 249，p = 0.0003）主要是由于骨折患者中ss基因型的过度表达（14.3%对1.4%），相当于ss基因型患者椎骨骨折的优势比为11.83（95%置信区间2.64-52.97）。在男性（χ2 = 11.52，n = 95，p = 0.0032，OR = 2.04）和女性（χ2 = 6.90，n = 154，p = 0.032，OR = 1.37）中，两组间的基因型分布差异相似。与上述一致，logistic回归分析显示ss基因型是骨质疏松性骨折的独立预测因子（p = 0.028）。这项研究证实了COLIA 1 Sp1多态性与腰椎骨折显著相关。这种关联在男性和女性中都可以看到，对骨折风险的影响似乎部分独立于骨矿物质密度。我们的研究结果提高了在Sp1位点的基因分型可能在识别男性和女性中有骨折风险的个体方面具有临床价值的可能性。
Genetic factors play an important role in the pathogenesis of osteoporosis, and recent studies have shown that a polymorphic Sp1 binding site in collagen type I α1 (COLIA1) gene is associated with bone mass and vertebral fractures in women from the U.K. Information on the predictive value of the COLIA1 Sp1 polymorphism in other populations is limited, however, and no studies have yet been performed in osteoporotic males. In view of this, we analyzed COLIA1 genotypes in relation to bone density and biochemical markers of bone turnover and the presence of osteoporotic fractures in a case‐control study of Danish men and women. COLIA1 genotype was determined by polymerase chain reaction analysis of genomic DNA extracted from peripheral blood samples and related to bone mass, biochemical markers of bone turnover, and the presence of fracture in a study of 375 osteoporotic vertebral fracture patients and normal controls. There was no significant effect of COLIA1 genotype on bone mass or biochemical markers when data from the control group (n = 195) and fracture group (n = 180) were analyzed separately. However, the genotype distribution was significantly different in the fracture cases compared with age‐matched controls (χ2 = 16.48, n = 249, p = 0.0003) due mainly to over‐representation of the ss genotype in the fracture patients (14.3% vs. 1.4%), equivalent to an odds ratio for vertebral fracture of 11.83 (95% confidence interval 2.64–52.97) in those with the ss genotype. Similar differences in genotype distribution between osteoporotic patients and controls were observed in both men (χ2 = 11.52, n = 95, p = 0.0032, OR = 2.04) and women (χ2 = 6.90, n = 154, p = 0.032, OR = 1.37). In keeping with the above, logistic regression analysis showed that the ss genotype was an independent predictor of osteoporotic fracture (p = 0.028). This study confirms that the COLIA1 Sp1 polymorphism is significantly associated with osteoporotic vertebral fractures. The association is seen in both men and women, and the effect on fracture risk appears to be partly independent of bone mineral density. Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying individuals at risk of osteoporotic fractures in both genders.