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Common genetic variation in the DKK1 gene is associated with hip axis length but not with bone mineral density and bone turnover markers in young adult men: results from the Odense Androgen Study.

https://arctichealth.org/en/permalink/ahliterature145854
Source
Calcif Tissue Int. 2010 Apr;86(4):271-81
Publication Type
Article
Date
Apr-2010
Author
Elke Piters
Wendy Balemans
Torben Leo Nielsen
Marianne Andersen
Eveline Boudin
Kim Brixen
Wim Van Hul
Author Affiliation
Department of Medical Genetics, University of Antwerp and University Hospital, Antwerp, Belgium. elke.piters@ua.ac.be
Source
Calcif Tissue Int. 2010 Apr;86(4):271-81
Date
Apr-2010
Language
English
Publication Type
Article
Keywords
Adult
Biological Markers - analysis - metabolism
Body Weights and Measures
Bone Density - genetics
Bone Remodeling - genetics
Cohort Studies
Denmark
Epistasis, Genetic
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation - physiology
Hip - anatomy & histology
Hip Fractures - genetics
Humans
Intercellular Signaling Peptides and Proteins - genetics
Linkage Disequilibrium
Male
Polymorphism, Single Nucleotide - physiology
Young Adult
Abstract
LRP5 was recently confirmed as an important susceptibility gene for osteoporosis. Our objective was to evaluate the effect of DKK1 polymorphisms on bone mineral density (BMD), hip geometry, and bone turnover. DKK1 is a secreted protein that binds to LRP5/6 receptors and inhibits canonical Wnt signaling. Using HapMap, we selected three SNPs covering the genetic variation in a 13.53-kb region comprising DKK1. The Odense Androgen Study is a population-based study comprising 783 Caucasian men aged 20-29 years. BMD and hip structural parameters were available for study. Bone turnover markers were used as a secondary end point. All analyses were repeated after adjusting for covariables and in subgroups according to physical activity. We found no significant association between DKK1 and BMD or markers of bone turnover; however, a significant association (P = 0.012) was found for rs1569198 with hip axis length (HAL), independent of BMD and height. Moreover, the association seemed to be driven by the non-sedentary subgroup (P = 0.004). Haplotype analysis further confirmed the association of rs1569198 with HAL. Furthermore, we obtained indications for interaction between DKK1 and LRP5 genotypes for different hip geometry parameters. As almost all variance within the DKK1 gene was covered, we conclude that common variation in this gene does not markedly influence BMD or bone turnover markers in young men. In this population, however, a common SNP in DKK1 does have a significant effect on HAL, implying a possible effect on hip fracture risk in the general population. This finding could be of interest but needs replication in independent populations.
PubMed ID
20101398 View in PubMed
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Relation of PvuII site polymorphism in the COL1A2 gene to the risk of fractures in prepubertal Finnish girls.

https://arctichealth.org/en/permalink/ahliterature184882
Source
Physiol Genomics. 2003 Aug 15;14(3):217-24
Publication Type
Article
Date
Aug-15-2003
Author
Miia Suuriniemi
Anitta Mahonen
Vuokko Kovanen
Markku Alén
Sulin Cheng
Author Affiliation
Department of Cell Biology, University of Jyväskylä, Finland.
Source
Physiol Genomics. 2003 Aug 15;14(3):217-24
Date
Aug-15-2003
Language
English
Publication Type
Article
Keywords
Binding Sites - genetics
Bone Density - genetics
Bone Remodeling - genetics
Child
Collagen - genetics
Collagen Type I
Deoxyribonucleases, Type II Site-Specific - genetics
Female
Finland - epidemiology
Fractures, Bone - epidemiology - genetics
Genetic Predisposition to Disease - genetics
Humans
Polymorphism, Genetic - genetics
Polymorphism, Single Nucleotide
Puberty - genetics
Retrospective Studies
Risk factors
Abstract
Genetic susceptibility to fractures may be detectable in early childhood. We evaluated the associations between the polymorphic PvuII site of the COL1A2 gene and bone properties assessed by different modalities (dual-energy X-ray absorptiometry; peripheral quantitative computed tomography; gel coupling scanning quantitative ultrasonometry; ultrasound bone sonometry), bone turnover markers, and the occurrence of fractures in 244 prepubertal Finnish girls. Tanner stage and physical characteristics did not differ significantly among girls with different COL1A2 genotypes. The polymorphism was not significantly associated with different bone properties or any of the bone turnover markers when girls at Tanner stage I (prepuberty) and stage II (early puberty) were considered together, but there was a significant association with spine bone mineral content (BMC) and bone mineral density (BMD), as well as with speed of sound (SOS) (P
PubMed ID
12813128 View in PubMed
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Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls.

https://arctichealth.org/en/permalink/ahliterature81633
Source
J Bone Miner Metab. 2006;24(4):329-36
Publication Type
Article
Date
2006
Author
Cusack Siobhan
Mølgaard Christian
Michaelsen Kim F
Jakobsen Jette
Lamberg-Allardt Christel J E
Cashman Kevin D
Author Affiliation
Department of Food and Nutritional Sciences, University College, Cork, Ireland.
Source
J Bone Miner Metab. 2006;24(4):329-36
Date
2006
Language
English
Publication Type
Article
Keywords
Age Factors
Biological Markers
Bone Density - genetics
Bone Remodeling - genetics
Child
Denmark
Densitometry, X-Ray
Estrogen Receptor alpha - genetics
Female
Genotype
Humans
Receptors, Calcitriol - genetics
Abstract
Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and estrogen receptor-alpha (ERalpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ERalpha genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary and environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ERalpha genotypes were associated (P
PubMed ID
16816928 View in PubMed
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