摘要

Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes.Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups (p < 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), (p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses.Allowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases.

译文

骨质疏松症和骨折风险被认为是在基因控制之下。正在进行大量的工作来确定确定这种风险的确切基因变异。先前的研究表明影响 COLIA1 基因 Sp1 结合位点的 G/T 多态性是低骨密度 (BMD) 和骨质疏松性骨折的遗传标记,但是还没有关于 COLIA1 等位基因与这些表型相关的非常大规模的研究。在这里,我们评估了 COLIA1 Sp1 等位基因作为 BMD 和骨折预测因子的作用,该多中心研究涉及来自几个欧洲国家的 20,786 人。在股骨颈处,平均 (95% 置信区间 [CI]) BMD 值为 25 mg/cm2 (CI,16 至 34 mg/cm2) TT 纯合子低于其他基因型组 (p <0.001),在腰椎观察到类似的差异; 21 mg/cm2 (CI,1 至 42 mg/cm2),(p = 0.039)。在对潜在混杂因素进行调整后,这些关联没有改变。在未经调整或调整的分析中,总体上与骨折无关 (比值比 [OR] = 1.01 [CI,0.95-1.08]), 但是在女性中,与脊椎骨折和名义上显著的与偶发的脊椎骨折相关的趋势并不显著 (OR = 1.33 [CI,1.00 到 1.77]) 独立于 BMD,并且在调整后的分析中没有改变。考虑到参与团队之间不可避免的异质性,据我们所知,这项研究是骨质疏松遗传学领域有史以来针对单一基因进行的最大规模的研究,表明 COLIA1 Sp1 多态性与骨密度降低相关,并可能导致椎体事件女性骨折, 独立于 BMD。然而,我们观察到的关联并不大,这表明了进行研究的重要性,这些研究有足够的能力来检测和量化常见基因变异对复杂疾病的影响。

Osteoporosis

内分泌 内分泌相关 疾病
概述  :  

骨质疏松症是一种疾病,其中骨骼弱化增加了断骨风险,这是老年人骨折的最常见原因,直到骨折发生,通常没有任何症状。骨质疏松症可能是由于最大骨量低于正常值和骨量高于正常值所致,绝经后由于雌激素水平降低,骨质流失增加。骨质疏松症也可能由于多种疾病治疗而发生,包括酒精中毒,厌食,甲状腺功能亢进,肾脏疾病和卵巢手术切除等。某些药物会增加骨质流失的速度,包括一些抗癫痫药,化学疗法,质子泵抑制剂,选择性血清素再摄取抑制剂和糖皮质激素。吸烟和太少运动也是危险因素,骨质疏松症的定义是骨密度比年轻成年人的骨密度低

Osteoporosis   英/ˌɒstiəʊpəˈrəʊsɪs/   美/ˌɑːstioʊpəˈroʊsɪs/

释    义   n. [外科] 骨质疏松症

例    句   DEXA scans help find out whether you have osteoporosis or are at risk of developing it. 地塞米松扫描有助于了解您是否有骨质疏松症或处于危险的发展。

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