A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women
2004 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, no 12, 6173-6178 p.Article in journal (Refereed) Published
Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor a (ERa). RIZ1 has previously been shown to be a specific ERa coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704+/- of a proline at position 704) to coactivate the ERa and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERa in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704+/-) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704+/- group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.
Place, publisher, year, edition, pages
2004. Vol. 89, no 12, 6173-6178 p.
Adult, Bone Density/*genetics, Cohort Studies, DNA-Binding Proteins/*genetics, Estrogen Receptor alpha/*metabolism, Female, Gene Deletion, Genotype, Humans, Nuclear Proteins/*genetics, Polymorphism; Genetic, Random Allocation, Sweden, Transcription Factors/*genetics
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-14741DOI: 10.1210/jc.2004-0403PubMedID: 15579774OAI: oai:DiVA.org:uu-14741DiVA: diva2:42512