title: 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.
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.
authors.affiliation: Department of Medical Genetics, University and University Hospital of Antwerp, Prins Boudewijnlaan 43B, 2650 Edegem, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Piters
authors.forename: Fenna
authors.initials: F
authors.lastname: de Freitas
authors.forename: Torben Leo
authors.initials: TL
authors.lastname: Nielsen
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersen
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015331:Cohort Studies; D003718:Denmark; D005272:Femur Neck / Q000502:physiology; D056726:Genetic Association Studies; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C422903:SOST protein, human