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Variation in the bone morphogenetic protein-2 gene: effects on fat and lean body mass in young and elderly women

¹ Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences Malmö, Lund University, 205 02 Malmö, Sweden² Department of Orthopaedics, Malmö University Hospital, 205 02 Malmö, Sweden³ Department of Orthopaedics, Karolinska University Hospital, S-171 76 Stockholm, Sweden⁴ Medical Genetics Unit, Department of Clinical Sciences Malmö, Lund University, 205 20 Malmö, Sweden

(Correspondence should be addressed to K Åkesson; Email: kristina.akesson{at}med.lu.se)

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.

Design: 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.