Eight genes are highly associated with BMD variation in postmenopausal Caucasian women
| Autor: | Arnoldo Frigessi, Finn P. Reinholt, Vigdis T. Gautvik, Rune Jemtland, Marit Holden, Per I. Høvring, Hilde Refvem, Sjur Reppe, Ole Kristoffer Olstad, Kaare M. Gautvik |
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| Rok vydání: | 2010 |
| Předmět: |
Genetic Markers
medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism Osteoporosis Biology White People Bone remodeling Cohort Studies chemistry.chemical_compound Absorptiometry Photon Bone Density Internal medicine medicine Humans Risk factor Osteoporosis Postmenopausal Aged Oligonucleotide Array Sequence Analysis Aged 80 and over Bone mineral Genetic Variation Middle Aged medicine.disease Postmenopause Gene expression profiling Leukemia Endocrinology chemistry Sclerostin Female Body mass index |
| Zdroj: | Bone. 46:604-612 |
| ISSN: | 8756-3282 |
| Popis: | Low bone mineral density (BMD) is an important risk factor for skeletal fractures which occur in about 40% of women >/=50 years in the western world. We describe the transcriptional changes in 84 trans-iliacal bone biopsies associated with BMD variations in postmenopausal females (50 to 86 years), aiming to identify genetic determinants of bone structure. The women were healthy or having a primary osteopenic or osteoporotic status with or without low energy fractures. The total cohort of 91 unrelated women representing a wide range of BMDs, were consecutively registered and submitted to global gene Affymetrix microarray expression analysis or histomorphometry. Among almost 23,000 expressed transcripts, a set represented by ACSL3 (acyl-CoA synthetase long-chain family member 3), NIPSNAP3B (nipsnap homolog 3B), DLEU2 (Deleted in lymphocytic leukemia, 2), C1ORF61 (Chromosome 1 open reading frame 61), DKK1 (Dickkopf homolog 1), SOST (Sclerostin), ABCA8, (ATP-binding cassette, sub-family A, member 8), and uncharacterized (AFFX-M27830-M-at), was significantly correlated to total hip BMD (5% false discovery rate) explaining 62% of the BMD variation expressed as T-score, 53% when adjusting for the influence of age (Z-score) and 44% when further adjusting for body mass index (BMI). Only SOST was previously associated to BMD, and the majority of the genes have previously not been associated with a bone phenotype. In molecular network analyses, SOST shows a strong, positive correlation with DKK1, both being members of the Wnt signaling pathway. The results provide novel insight in the underlying biology of bone metabolism and osteoporosis which is the ultimate consequence of low BMD. |
| Databáze: | OpenAIRE |
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