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Comparative transcriptome analysis identifies CARM1 and DNMT3A as genes associated with osteoporosis.

ABSTRACT: To identify new candidate genes in osteoporosis, mainly involved in epigenetic mechanisms, we compared whole gene-expression in osteoblasts (OBs) obtained from women undergoing hip replacement surgery due to fragility fracture and severe osteoarthritis. Then, we analyzed the association of several SNPs with BMD in 1028 women. Microarray analysis yielded 2542 differentially expressed transcripts belonging to 1798 annotated genes, of which 45.6% (819) were overexpressed, and 54.4% (979) underexpressed (fold-change between?-?7.45 and 4.0). Among the most represented pathways indicated by transcriptome analysis were chondrocyte development, positive regulation of bone mineralization, BMP signaling pathway, skeletal system development and Wnt signaling pathway. In the translational stage we genotyped 4 SNPs in DOT1L, HEY2, CARM1 and DNMT3A genes. Raw data analyzed against inheritance patterns showed a statistically significant association between a SNP of DNMT3A and femoral neck-(FN) sBMD and primarily a SNP of CARM1 was correlated with both FN and lumbar spine-(LS) sBMD. Most of these associations remained statistically significant after adjusting for confounders. In analysis with anthropometric and clinical variables, the SNP of CARM1 unexpectedly revealed a close association with BMI (p?=?0.000082), insulin (p?=?0.000085), and HOMA-IR (p?=?0.000078). In conclusion, SNPs of the DNMT3A and CARM1 genes are associated with BMD, in the latter case probably owing to a strong correlation with obesity and fasting insulin levels.

SUBMITTER: Panach L

PROVIDER: S-EPMC7530982 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Comparative transcriptome analysis identifies CARM1 and DNMT3A as genes associated with osteoporosis.

Panach Layla L Pertusa Clara C Martínez-Rojas Beatriz B Acebrón Álvaro Á Mifsut Damián D Tarín Juan J JJ Cano Antonio A García-Pérez Miguel Ángel MÁ

Scientific reports 20201001 1

To identify new candidate genes in osteoporosis, mainly involved in epigenetic mechanisms, we compared whole gene-expression in osteoblasts (OBs) obtained from women undergoing hip replacement surgery due to fragility fracture and severe osteoarthritis. Then, we analyzed the association of several SNPs with BMD in 1028 women. Microarray analysis yielded 2542 differentially expressed transcripts belonging to 1798 annotated genes, of which 45.6% (819) were overexpressed, and 54.4% (979) underexpre ...[more]

PMID: 33004909

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Comparative transcriptome analysis identifies CARM1 and DNMT3A as genes associated with osteoporosis.

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Comparative transcriptome analysis identifies CARM1 and DNMT3A as genes associated with osteoporosis.

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