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Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts.

https://arctichealth.org/en/permalink/ahliterature128687
Source
Mol Genet Metab. 2012 Mar;105(3):508-15
Publication Type
Article
Date
Mar-2012
Author
Eveline Boudin
Elke Piters
Erik Fransen
Torben Leo Nielsen
Marianne Andersen
Greet Roef
Youri Taes
Kim Brixen
Wim Van Hul
Author Affiliation
Department of Medical Genetics, University of Antwerp, Belgium. eveline.boudin@ua.ac.be
Source
Mol Genet Metab. 2012 Mar;105(3):508-15
Date
Mar-2012
Language
English
Publication Type
Article
Keywords
Adiposity - genetics
Adult
Aged
Belgium
Body Composition - genetics
Body mass index
Bone Density - genetics
Bone and Bones - physiology
Cohort Studies
Denmark
European Continental Ancestry Group - genetics
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Intercellular Signaling Peptides and Proteins - genetics
Male
Membrane Proteins - genetics
Middle Aged
Osteoporosis - genetics
Polymorphism, Single Nucleotide
Young Adult
Abstract
Bone mineral density (BMD) and bone strength are predictive parameters for the development of osteoporosis and related fracture later in life. Although it is well known that BMD and bone strength have a high heritability, not much of the variation is already explained. Mice models showed that sFRP1 has an influence on bone formation. Therefore this study aimed to investigate the effect of common genetic variation on BMD and bone strength in Caucasian men of different ages. Using HapMap we selected 13 tagSNPs which tag most common genetic variation in and around sFRP1 and we genotyped these SNPs in the young cohort of the Odense Androgen Study (OAS). The OAS includes a total of 1383 Danish men from two different age groups ([20-29 years]: N=783; [60-74 years]: N=600) and is well characterised. The subjects were phenotyped for BMD at several sites, and additionally for body composition and hip geometry parameters. Based on the results of the young cohort we selected three SNPs for further analysis in the complete OAS population. To conclude we tried to replicate the results of two SNPs in an independent population of 994 Belgian men. We found a strong association for rs9694405 with BMI as well in both cohorts separately as in the whole OAS population. Further we found rs4736965 associated with several hip geometry parameters in the same population. However we were not able to replicate those results in the Belgian population. At last we found in the OAS population age specific effects for rs10106678 with whole body BMD and waist to hip ratio.
PubMed ID
22178351 View in PubMed
Less detail

Association study of polymorphisms in the SOST gene region and parameters of bone strength and body composition in both young and elderly men: data from the Odense Androgen Study.

https://arctichealth.org/en/permalink/ahliterature129727
Source
Calcif Tissue Int. 2012 Jan;90(1):30-9
Publication Type
Article
Date
Jan-2012
Author
Elke Piters
Fenna de Freitas
Torben Leo Nielsen
Marianne Andersen
Kim Brixen
Wim Van Hul
Author Affiliation
Department of Medical Genetics, University and University Hospital of Antwerp, Prins Boudewijnlaan 43B, 2650 Edegem, Belgium.
Source
Calcif Tissue Int. 2012 Jan;90(1):30-9
Date
Jan-2012
Language
English
Publication Type
Article
Keywords
Adult
Aged
Body Composition - genetics
Body mass index
Bone Density - genetics
Bone Morphogenetic Proteins - genetics
Cohort Studies
Denmark
Femur Neck - physiology
Genetic Association Studies
Genetic Markers - genetics
Genotype
Humans
Low Density Lipoprotein Receptor-Related Protein-5 - genetics
Male
Middle Aged
Polymorphism, Genetic
Abstract
By means of different genetic association studies the SOST gene, encoding sclerostin, has repeatedly been suggested to regulate bone mineral density (BMD) and osteoporosis susceptibility. This study aimed at a further understanding of the importance of two previously studied single-nucleotide polymorphisms in the SOST gene, rs10534024 (SRP3) and rs9902563 (SRP9), in the Odense Androgen Study (OAS) cohort. This cohort includes a total of 1,383 Danish men from two different age groups, 20-29 years (n = 783) and 60-74 years (n = 600), and is well characterized. Subjects were phenotyped for BMD at several sites and additionally for body composition and hip geometric parameters. In a combined analysis of the young and the elderly OAS, no associations were found for SRP3 either with BMD or with hip geometry. Instead, we found that this polymorphism had a relatively large effect on weight (-1.149 kg) and body mass index (-0.389 kg/m(2)) (P = 0.021 and 0.006 under a codominant model). For SRP9, a significant association was found for femoral neck BMD (+0.020 g/cm(2), P = 0.020) and a trend toward significance for hip geometry (buckling ratio of the narrow neck) but only when considering a recessive effect of the minor allele (C). No age-specific effects were found for either of the two SNPs. In summary, we are the first to find interesting associations between SRP3 and body composition. For SRP9, we replicated a site-specific association with femoral neck BMD. In addition, we report a novel association for this polymorphism with hip geometry.
PubMed ID
22076526 View in PubMed
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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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Single nucleotide polymorphisms in sFRP4 are associated with bone and body composition related parameters in Danish but not in Belgian men.

https://arctichealth.org/en/permalink/ahliterature124236
Source
Mol Genet Metab. 2012 Jul;106(3):366-74
Publication Type
Article
Date
Jul-2012
Author
Eveline Boudin
Elke Piters
Torben Leo Nielsen
Marianne Andersen
Greet Roef
Youri Taes
Kim Brixen
Wim Van Hul
Author Affiliation
Department of Medical Genetics, University of Antwerp, Belgium. eveline.boudin@ua.ac.be
Source
Mol Genet Metab. 2012 Jul;106(3):366-74
Date
Jul-2012
Language
English
Publication Type
Article
Keywords
Adult
Aged
Belgium
Body Composition - genetics
Bone Density - genetics
Bone and Bones
Cohort Studies
Denmark
Genetic Variation
Genotype
Hip - physiology
Hip Fractures - ethnology - genetics
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins - genetics
Abstract
The senescence accelerated mouse P6 (SAMP6) has a low bone mass and has previously shown to be a good model for senile osteoporosis in humans. In addition to a reduced bone mass, SAMP6 mice are obese and have hyperlipidemia. Using positional cloning and expression studies, an increased expression of sfrp4 was found in these mice. SFRP4 is a modulator of the Wnt signalling pathway. This pathway has been previously shown to be involved in regulating bone mass. Additional evidence that sFRP4 has an influence on BMD was delivered by linkage and association studies mostly performed in Asian populations. Based on these data we decided to perform an association study between common variants in sFRP4, BMD, hip geometry parameters and body composition parameters in a population consisting of 1383 Danish men (783 aged 20-29 years; 600 aged 60-74 years). Afterwards we tried to replicate the significant results in a population of 994 Belgian men. In the Danish population we found 6 SNPs associated with BMD at the hip and/or femoral neck. Furthermore, all 6 SNPs were associated with several hip geometry parameters. The homozygous presence of the minor allele resulted for all SNPs (except rs4720265) in a decrease in bone density and bone strength. Finally, we observed in the Danish population age specific associations with height and fat mass. In the Belgian population we tried to replicate the results of three SNPs with BMD and body composition parameters. Unfortunately, we were not able to replicate the results found in the Danish cohort but we found one SNP (rs2598116) associated with height. In conclusion, genetic variation in sFRP4 has an influence on hip fracture risk, percentage body fat and height in a Danish male population. However, we were unable to replicate these results in an independent Belgian population.
PubMed ID
22608881 View in PubMed
Less detail