Schoofs Mariette W C J, van der Klift Marjolein, Hofman Albert, van Duijn Cornelia M, Stricker Bruno H Ch, Pols Huibert A P, Uitterlinden André G
Department of Internal Medicine, Erasmus Medical Center, Rotterdam 300 DR, The Netherlands.
J Bone Miner Res. 2004 Sep;19(9):1490-6. doi: 10.1359/JBMR.040605. Epub 2004 Jun 21.
To study the association between the ApoE gene polymorphism and osteoporosis, we performed an association study in 5,857 subjects from the Rotterdam Study. We did not observe an association between the ApoE polymorphism and osteoporosis in this study, which is thus far the largest study on ApoE and osteoporosis.
The E4 allele of the E2, E3, E4 protein isoform polymorphism in the gene encoding apolipoprotein E (ApoE) has previously been associated with an increased fracture risk. We investigated the association between the ApoE polymorphism and BMD, bone loss, and incident fractures as part of the Rotterdam Study a prospective population-based cohort study of diseases in the elderly.
The study population consisted of 5,857 subjects (2,560 men; 3,297 women) for whom data on ApoE genotypes, confounding variables, and follow-up of nonvertebral fractures were available. Data on femoral neck and lumbar spine BMD were available for 4,814 participants. Genotype analyses for bone loss (defined as annualized percent change in BMD at the hip and lumbar spine) and BMD were performed using ANOVA. Fractures were analyzed using a Cox proportional-hazards model and logistic regression. All relative risks were adjusted for age and body mass index.
The genotype distribution of the study population was in Hardy-Weinberg equilibrium (p = 0.98) and did not differ by gender. At baseline, mean BMD of the lumbar spine and femoral neck did not differ between the ApoE genotypes of men and women. Bone loss (mean follow-up, 2.0 years) did not differ by ApoE genotype for women and men. During a mean follow-up of 6.6 years, 708 nonvertebral fractures (198 hip fractures and 179 wrist fractures) and 149 incident vertebral fractures occurred. No consistent differences in the distribution of alleles could be observed between subjects with or without these fractures. Our data do not support the hypothesis that the ApoE*4 risk allele is associated with BMD, increased bone loss, or an increased risk of osteoporotic fractures.
为研究载脂蛋白E（ApoE）基因多态性与骨质疏松症之间的关联，我们在鹿特丹研究的5857名受试者中开展了一项关联研究。在本研究中，我们未观察到ApoE多态性与骨质疏松症之间存在关联，这是迄今为止关于ApoE与骨质疏松症的最大规模研究。
载脂蛋白E（ApoE）基因编码的E2、E3、E4蛋白异构体多态性中的E4等位基因，此前已被证实与骨折风险增加有关。作为鹿特丹研究（一项针对老年人疾病的前瞻性人群队列研究）的一部分，我们调查了ApoE多态性与骨密度（BMD）、骨质流失及新发骨折之间的关联。
研究人群包括5857名受试者（2560名男性；3297名女性），他们拥有ApoE基因型、混杂变量及非椎体骨折随访数据。4814名参与者拥有股骨颈和腰椎骨密度数据。使用方差分析（ANOVA）对骨质流失（定义为髋部和腰椎骨密度的年化变化百分比）和骨密度进行基因型分析。采用Cox比例风险模型和逻辑回归分析骨折情况。所有相对风险均根据年龄和体重指数进行了调整。
研究人群的基因型分布符合哈迪-温伯格平衡（p = 0.98），且不存在性别差异。在基线时，男性和女性的ApoE基因型之间，腰椎和股骨颈的平均骨密度无差异。男性和女性的骨质流失（平均随访2.0年）在ApoE基因型之间无差异。在平均6.6年的随访期间，发生了708例非椎体骨折（198例髋部骨折和179例腕部骨折）以及149例新发椎体骨折。在有或无这些骨折的受试者之间，未观察到等位基因分布存在一致差异。我们的数据不支持ApoE*4风险等位基因与骨密度、骨质流失增加或骨质疏松性骨折风险增加相关的假设。
