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, 20-29years (n=783) and 60-74years (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 (-1.149kg) and body mass index (-0.389kg/m(2)) (P=0.021 and 0.006 under a codominant model). For SRP9, a significant association was found for femoral neck BMD (+0.020g/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.