Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil; Programa de Pós-Graduação em Biotecnologia, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
Aging Cell Biology Laboratory, Department of Morphology, Health Sciences Center, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
J Clin Densitom. 2018 Apr-Jun;21(2):227-235. doi: 10.1016/j.jocd.2017.03.005. Epub 2017 Aug 4.
Osteoporosis is one of the major diseases that affects mostly postmenopausal women. Despite being a multifactorial disease, some genes have been shown to play an important role in osteoporosis. Bone mineral density (BMD) is still largely used to diagnose it, although many other biomarkers are used to better follow the disease onset. It has been shown that the apolipoprotein E (APOE) gene could be a biomarker for risk of fractures as well as to predict lower BMD in patients with osteoporosis. The human APOE gene encodes 3 protein isoforms called ApoE2, ApoE3, and ApoE4, resulting in 4 possible genotypes, because they are a product of a single nucleotide polymorphism found in this gene. So far, the APOE4 allele has been associated with low BMD in postmenopausal women and to incidence of bone breaking in older women. This study aimed to investigate the role of ApoE isoforms in a cohort of 413 postmenopausal Brazilian women. These patients were randomly recruited, clinically examined, and subjected to dual-energy X-ray absorptiometry to measure their BMD. Patients were further grouped as normal BMD (T-score < 0.5) or low BMD (T-score > 1.0, osteopenic or osteoporotic). Patients with osteopenia or osteoporosis were further genotyped for APOE alleles as well as tested for many serum bone turnover biomarkers. Our data showed that presence of the APOE3 allele was associated with both higher BMDs and higher serum concentrations of osteocalcin and alkaline phosphatase, biomarkers for bone formation. On the other hand, the APOE2 and APOE4 alleles were associated with lower BMD as well as higher levels of serum C-terminus collagen peptide and urinary deoxipyridinolines, biomarkers for bone resorption. However, these effects on lower BMD and bone resorption biomarkers observed in either APOE2 or APOE4 alleles were eliminated when patients' genotype carried the APOE3 allele. Codominance of the APOE3 allele was also associated with lesser cases of bone fractures in these patients within a 5-year follow-up. In conclusion, our data show that APOE4 may be associated with lower bone formation as well as increased risk of osteoporosis and bone fractures, whereas APOE3 seems to decrease lowering BMD in postmenopausal women, and its presence seemed to lower the incidence of bone breaking in patients with osteoporosis.
骨质疏松症是影响绝经后妇女的主要疾病之一。尽管骨质疏松症是一种多因素疾病，但已有一些基因被证明在其中起着重要作用。骨密度（BMD）仍然主要用于诊断骨质疏松症，尽管还有许多其他生物标志物用于更好地跟踪疾病的发生。已经表明载脂蛋白 E（APOE）基因可以作为骨折风险的生物标志物，并预测骨质疏松症患者的 BMD 较低。人类 APOE 基因编码 3 种蛋白异构体，称为 ApoE2、ApoE3 和 ApoE4，导致 4 种可能的基因型，因为它们是该基因中发现的单个核苷酸多态性的产物。到目前为止，APOE4 等位基因与绝经后妇女的低 BMD 以及老年妇女的骨折发生率有关。本研究旨在调查 ApoE 异构体在 413 名绝经后巴西女性队列中的作用。这些患者是随机招募的，经过临床检查，并进行双能 X 线吸收法测量他们的 BMD。患者进一步分为正常 BMD（T 评分 < 0.5）或低 BMD（T 评分 > 1.0，骨质减少或骨质疏松）。骨质减少或骨质疏松症患者进一步进行 APOE 等位基因分型，并检测许多血清骨转换生物标志物。我们的数据表明，APOE3 等位基因的存在与更高的 BMD 和更高的血清骨钙素和碱性磷酸酶浓度有关，这些标志物是骨形成的标志物。另一方面，APOE2 和 APOE4 等位基因与较低的 BMD 以及更高的血清 C 端胶原蛋白肽和尿脱氧吡啶啉水平有关，这些标志物是骨吸收的标志物。然而，当患者的基因型携带 APOE3 等位基因时，观察到 APOE2 或 APOE4 等位基因对较低 BMD 和骨吸收生物标志物的这些影响就会消除。APOE3 等位基因的共显性也与这些患者在 5 年随访期间较少发生骨折有关。总之，我们的数据表明 APOE4 可能与较低的骨形成以及骨质疏松症和骨折风险增加有关，而 APOE3 似乎会降低绝经后妇女的 BMD，并降低骨质疏松症患者骨折的发生率。
