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J Bone Miner Res. 2018 Nov;33(11):1980-1989. doi: 10.1002/jbmr.3527. Epub 2018 Jul 20.

Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women.

Author information

1
Department of Pharmacology and Therapeutics, McGill University Health Center, Montreal, QC, Canada.
2
Department of Medicine, McGill University Health Center, Montreal, QC, Canada.

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.

KEYWORDS:

BLOOD DNA; DNA METHYLATION; EPIGENETIC SIGNATURE; OSTEOPOROSIS; POSTMENOPAUSAL WOMEN

PMID:
29924424
DOI:
10.1002/jbmr.3527

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