Variation in the bone morphogenetic protein-2 gene: effects on fat and lean body mass in young and elderly women.
OBJECTIVE
Bone morphogenetic protein-2 (BMP2) plays a critical role in osteoblastogenesis and adipogenesis from osteoprogenitor cells. The balance between osteogenic and adipogenic effects is influenced by BMP2 concentration, transcription factors and age. BMP2 single nucleotide polymorphisms (SNPs) may contribute to osteoporosis risk, but the relationship between adiposity and body composition has not been explored. We investigated the relationship between BMP2 polymorphisms and body composition in young and elderly women.


METHODS
Population-based association study.


METHODS
Four BMP2 SNPs studied. Total body fat and lean mass measured by DEXA in two cohorts: 'PEAK-25' women aged 25 (+/-0.00) (n=993) and osteoporosis prospective risk assessment (OPRA) women aged 75 (+/-0.00) years (n=1001).


RESULTS
We found no association between BMP2 SNPs and fat or lean mass, however, we observed consistent although non-significant trends. Polymorphisms, rs235767 and Ser37Ala, exerted opposing effects on most parameters of soft tissue and bone mass in both cohorts. This relationship appeared to be age specific with large differences between alleles observed (fat mass; Ser37Ala: 14.3% (PEAK-25), -3.5% (OPRA)). These initial results appear to suggest that alleles exerting a beneficial effect in young women may subsequently contribute to phenotypes associated with osteoporosis risk in elderly women.


CONCLUSIONS
While further analyses in other comparative populations are necessary, in this study of almost 2000 women we observed interesting, although non-significant trends, regarding the effects of variation in the BMP2 gene on parameters of body mass. Although the exact nature of the relationship remains uncertain, we suggest that the mechanisms are influenced by age and environmental factors.
McGuigan
Fiona
F
Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, 205 02 Malmö, Sweden.
Larzenius
Emma
E
Callreus
Mattias
M
Gerdhem
Paul
P
Luthman
Holger
H
Akesson
Kristina
K
D000273:Adipose Tissue / Q000502:physiology; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001823:Body Composition / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006801:Humans; D010024:Osteoporosis / Q000453:epidemiology* / Q000235:genetics*; D050177:Overweight / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016212:Transforming Growth Factor beta / Q000235:genetics*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta