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The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Metabolic Bone Diseases)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Metabolic Bone Diseases)
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2007 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 6, 2300-2306 p.Article in journal (Refereed) Published
Abstract [en]

Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-α as well as ER-β. The specific ERα cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERα function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and crosssectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704+/+ genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704+/+ group than the P704-/- group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ERα cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.

Place, publisher, year, edition, pages
2007. Vol. 92, no 6, 2300-2306 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-14700DOI: 10.1210/jc.2006-1572ISI: 000247061700050PubMedID: 17356055OAI: oai:DiVA.org:uu-14700DiVA: diva2:42471
Available from: 2008-01-31 Created: 2008-01-31 Last updated: 2017-12-11Bibliographically approved

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Grundberg, ElinKindmark, AndreasLjunggren, ÖstenMallmin, HansBrändström, Helena

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