title: Single nucleotide polymorphisms in sFRP4 are associated with bone and body composition related parameters in Danish but not in Belgian men.
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.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Belgium. eveline.boudin@ua.ac.be
authors.forename: Eveline
authors.initials: E
authors.lastname: Boudin
authors.forename: Elke
authors.initials: E
authors.lastname: Piters
authors.forename: Torben Leo
authors.initials: TL
authors.lastname: Nielsen
authors.forename: Marianne
authors.initials: M
authors.lastname: Andersen
authors.forename: Greet
authors.initials: G
authors.lastname: Roef
authors.forename: Youri
authors.initials: Y
authors.lastname: Taes
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D000328:Adult; D000368:Aged; D001530:Belgium; D001823:Body Composition / Q000235:genetics*; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones; D015331:Cohort Studies; D003718:Denmark; D014644:Genetic Variation; D005838:Genotype; D006615:Hip / Q000502:physiology; D006620:Hip Fractures / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D011518:Proto-Oncogene Proteins; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins