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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women
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Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women

机译：绝经后妇女血液DNA骨质疏松症的表观遗传学鉴定

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ABSTRACT Osteoporosis is one of the most common age‐related progressive bone diseases in elderly people. Approximately one in three women and one in five men are predisposed to developing osteoporosis. In postmenopausal women, a reduction in BMD leads to an increased risk of fractures. In the current study, we delineated the DNA methylation signatures in whole blood samples of postmenopausal osteoporotic women. We obtained whole blood DNA from 22 normal women and 22 postmenopausal osteoporotic women (51 to 89 years old) from the Canadian Multicenter Osteoporosis Study (CaMos) cohort. These DNA samples were subjected to Illumina Infinium human methylation 450?K analysis. Illumina 450K raw data were analyzed by Genome Studio software. Analysis of the female participants with early and advanced osteoporosis resulted in the generation of a list of 1233 differentially methylated CpG sites when compared with age‐matched normal women. T test, ANOVA, and post hoc statistical analyses were performed, and 77 significantly differentially methylated CpG sites were identified. From the 13 most significant genes, ZNF267 , ABLIM2 , RHOJ , CDKL5 , and PDCD1 were selected for their potential role in bone biology. A weighted polygenic DNA methylation score of these genes predicted osteoporosis at an early stage with high sensitivity and specificity and correlated with measures of bone density. Pyrosequencing analysis of these genes was performed to validate the results obtained from Illumina 450?K methylation analysis. The current study provides proof of principal for the role of DNA methylation in osteoporosis. Using whole blood DNA methylation analysis, women at risk of developing osteoporosis can be identified before a diagnosis of osteoporosis is made using BMD as a screening method. Early diagnosis will help to select patients who might benefit from early therapeutic intervention. ? 2018 American Society for Bone and Mineral Research.
机译：摘要骨质疏松症是老年人中最常见的年龄相关的进步性骨病之一。在三个女性中大约一个人和五分之一的人倾向于发展骨质疏松症。在绝经后妇女中，BMD的减少导致骨折的风险增加。在目前的研究中，我们描绘了绝经后骨质疏松症妇女的全血样品中的DNA甲基化签名。我们从加拿大多中心骨质疏松研究（CAMOS）队列中，从22名正常妇女和22例绝经后骨质疏松症女性（51至89岁）获得了全血DNA。将这些DNA样品进行Illumina infinium人甲基化450〜K分析。 Illumina 450K原始数据被Genome Studio软件分析。与早期和晚期骨质疏松症的女性参与者分析导致与年龄匹配的正常女性相比产生1233个差异甲基化CPG位点的。进行测试，ANOVA和后HOC统计学分析，鉴定了77个显着差异差异的CPG位点。从13个最重要的基因，ZNF267，Ablim2，rhOJ，CDK15和PDCD1被选择用于它们在骨生物学中的潜在作用。这些基因的加权多基因DNA甲基化评分在早期患者预测骨质疏松症，具有高灵敏度和特异性，并与骨密度的测量相关。进行这些基因的焦点分析，以验证从Illumina 450α甲基化分析获得的结果。目前的研究提供了用于DNA甲基化在骨质疏松症中的作用的原则。使用全血DNA甲基化分析，可以在使用BMD作为筛选方法进行骨质疏松症的诊断之前鉴定出现骨质疏松症风险的妇女。早期诊断将有助于选择可能从早期治疗干预中受益的患者。还2018年美国骨骼和矿物学研究。

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