Langdahl B L, Ralston S H, Grant S F, Eriksen E F
Aarhus Bone and Mineral Research Group, University Department of Endocrinology, Aarhus University Hospital, Denmark.
J Bone Miner Res. 1998 Sep;13(9):1384-9. doi: 10.1359/jbmr.1998.13.9.1384.
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 alpha1 (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 (chi2 = 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 (chi2 = 11.52, n = 95, p = 0.0032, OR = 2.04) and women (chi2 = 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.
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α1（COLIA1）基因中的一个多态性Sp1结合位点与英国女性的骨量和椎体骨折有关。然而，关于COLIA1 Sp1多态性在其他人群中的预测价值的信息有限，并且尚未在骨质疏松男性中进行研究。有鉴于此，我们在一项丹麦男性和女性的病例对照研究中分析了COLIA1基因型与骨密度、骨转换生化标志物以及骨质疏松性骨折的存在之间的关系。通过对从外周血样本中提取的基因组DNA进行聚合酶链反应分析来确定COLIA1基因型，并将其与375例骨质疏松性椎体骨折患者和正常对照的骨量、骨转换生化标志物以及骨折情况相关联。当分别分析对照组（n = 195）和骨折组（n = 180）的数据时，COLIA1基因型对骨量或生化标志物没有显著影响。然而，与年龄匹配的对照组相比，骨折病例中的基因型分布有显著差异（χ2 = 16.48，n = 249，p = 0.0003），主要是因为骨折患者中ss基因型的比例过高（14.3%对1.4%），这相当于ss基因型的椎体骨折比值比为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，骨质疏松患者和对照组之间的基因型分布也观察到类似差异。与上述情况一致，逻辑回归分析表明ss基因型是骨质疏松性骨折的独立预测因子（p = 0.028）。本研究证实COLIA1 Sp1多态性与骨质疏松性椎体骨折显著相关。这种关联在男性和女性中均可见，并且对骨折风险的影响似乎部分独立于骨矿物质密度。我们的结果提出了在Sp1位点进行基因分型可能对识别男女骨质疏松性骨折风险个体具有临床价值的可能性。
