title: Lack of association between the SOST gene and bone mineral density in perimenopausal women: analysis of five polymorphisms.
abstract: Osteoporosis is a common disease characterized by a decrease in bone mass, architectural deterioration of the bone tissue, and an increased risk of fracture. The condition is under strong genetic control, involving a large variety of gene products, but to date the genes responsible remain poorly defined. Although population-based studies have identified polymorphisms in several candidate genes that are associated with bone mineral density (BMD), these account for only a small proportion of the population variance in bone mass. In this study, we looked for evidence of an allelic association between polymorphisms in the SOST gene and BMD. This gene was analyzed because loss-of-function mutations in SOST cause sclerosteosis, a sclerosing bone dysplasia associated with increased bone mass due to increased bone formation. We identified 26 different polymorphisms in the SOST gene and selected 5 of these for association analysis in a case-control study of 619 women with either high or low BMD, drawn from a random population-based survey of 5119 perimenopausal white women. The high BMD group comprised 326 women in whom lumbar spine BMD values adjusted for age, height, and weight were in the highest 16% of the population distribution, and the low BMD group comprised 293 women in whom BMD values were in the lowest 16% of the population distribution. The distribution of genotypes and alleles for each Single Nucleotide Polymorphism (SNP) examined did not differ in the low and high BMD groups. We conclude that, in this population, common allelic variations in the SOST gene do not contribute significantly to the regulation of high or low BMD.
authors.affiliation: Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Balemans
authors.forename: D
authors.initials: D
authors.lastname: Foernzler
authors.forename: C
authors.initials: C
authors.lastname: Parsons
authors.forename: M
authors.initials: M
authors.lastname: Ebeling
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: D M
authors.initials: DM
authors.lastname: Reid
authors.forename: K
authors.initials: K
authors.lastname: Lindpaintner
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
authors.forename: W
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density / Q000235:genetics*; D019485:Bone Morphogenetic Proteins; D002979:Climacteric; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D011506:Proteins; C422903:SOST protein, human