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- Bratteby, L E, et al.
(author)
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Whole-body mineral measurements in Swedish adolescents at 17 years compared to 15 years of age.
- 2002
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In: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 91:10, s. 1031-8
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Journal article (peer-reviewed)abstract
- AIM: To provide reference data for bone mineral variables in 15- and 17-y-old adolescents and to analyse the relationships between these variables and measures of bone and body size, gender, puberty, growth, various lifestyle and environmental factors and socioeconomic background.METHODS: In the same 321 randomly selected adolescents (147 boys and 174 girls) living in two different regions of Sweden, the total bone mineral content (TBMC), bone area (BA) and total bone mineral density (TBMD) were assessed by dual-energy X-ray absorptiometry at ages 15 and 17 y. The effects of bone and body size, gender, growth, sexual maturity, physical activity, region of domicile, social conditions, food habits, smoking and alcohol intake on TBMC and TBMD were examined in multivariate analyses.RESULTS: In the 15-y-old adolescents, BA, height, gender, physical activity, maturity and weight explained 91% and 48%, of the variance in TBMC and TBMD, respectively. In similar analyses in the 17-y-olds, the corresponding figures were 92% and 62%, respectively, when BA, height, growth, physical activity, gender and region emerged as significant in the model. In all these analyses, BA explained most of the variance in TBMC and TBMD. No significant reduction of variance was found when different measures of social conditions, smoking, food habits, alcohol or dietary intakes of energy, calcium or vitamin D were included in the models. The reason why region of domicile had a significant impact on TBMC in the 17-y-olds is not known. The fact that the normal fluoride concentration in drinking water (1.1 mg/L) is 10 times higher in the region where TBMC was higher than in the other region is an interesting observation.CONCLUSION: Almost 90% of the variance in TBMC and 50% of that in TBMD was explained by measures of bone and body size and only a few percent by gender, physical activity, Tanner stage, growth and region of domicile.
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- Grundberg, E, et al.
(author)
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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
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:12, s. 6173-6178
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Journal article (peer-reviewed)abstract
- 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.
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- Grundberg, E, et al.
(author)
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Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
- 2007
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In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:6, s. 829-837
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Journal article (peer-reviewed)abstract
- Summary Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. Introduction The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. Methods The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. Results When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. Conclusions Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.
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