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Single nucleotide polymorphisms in the human gene for osteoprotegerin are not related to bone mineral density or fracture in elderly women
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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2004 (English)In: Calcified Tissue International, ISSN 0171-967X, Vol. 74, no 1, 18-24 p.Article in journal (Refereed) Published
Abstract [en]

Osteoprotegerin (OPG), a secreted member of the tumor necrosis factor receptor family, is a potent inhibitor of osteoclast activation and differentiation. In animal models OPG prevents bone loss, and in humans bone resorption can be reduced by injections of OPG. OPG may also play a role in cardiovascular disease since mice lacking the OPG gene display arterial calcification. In a screening effort of the OPG gene, we recently discovered a single nucleotide polymorphism in the promoter region of OPG (T950C), and reported an association with vascular morphology and function in 59 healthy individuals. Due to the pronounced effect of OPG on bone turnover, the present study was conducted to investigate whether OPG polymorphisms are also associated with bone mineral density or with fracture. The relationship between single nucleotide polymorphisms in the promoter region of OPG (T950C) and the first intron (C1217T), and bone mineral density, measured by DXA in the hip or spine or ultrasound of the heel, was investigated in the Malmö OPRA-study of 1044 women, all 75 years old. The possible relation to fracture incidence was also analyzed. Among the 858 and 864 individuals respectively, genotyped, no significant associations between the investigated single nucleotide polymorphisms and bone mineral density measurements (T950C P = 0.50-0.64, C1217T P = 0.51-1.00), quantitative ultrasound measurements of the calcaneus, or fractures (T950C P = 0.61-0.66, C1217T P = 0.14-0.33) were found. Thus, our results show that polymorphisms in the OPG gene, one of which has previously been found to be associated with cardiovascular morphology and function, are not associated with bone mineral density in elderly Swedish women.

Place, publisher, year, edition, pages
2004. Vol. 74, no 1, 18-24 p.
Keyword [en]
Aged, Bone Density/*genetics, Calcaneus/ultrasonography, Cohort Studies, Female, Fractures; Spontaneous/epidemiology/*genetics, Glycoproteins/*genetics, Humans, Incidence, Introns, Osteoporosis; Postmenopausal/genetics, Osteoprotegerin, Polymorphism; Restriction Fragment Length, Polymorphism; Single Nucleotide, Promoter Regions (Genetics), Receptors; Cytoplasmic and Nuclear/*genetics, Receptors; Tumor Necrosis Factor, Sweden/epidemiology, Ultrasonography
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-14727DOI: 10.1007/s00223-002-2136-9PubMedID: 14508625OAI: oai:DiVA.org:uu-14727DiVA: diva2:42498
Available from: 2008-08-01 Created: 2008-08-01Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=14508625&dopt=Citation

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Brändström, HelenaStiger, FredrikMelhus, HåkanLjunggren, ÖstenKindmark, Andreas
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