Variation in the BMP2 Gene: Bone Mineral Density and Ultrasound in Young Adult and Elderly Women

Abstract

Bone morphogenetic protein-2 (BMP2) plays a key role in bone formation and maintenance. Studies of polymorphisms within the gene in relation to bone mineral density (BMD) and fracture have been inconsistent. Our aim was to investigate associations between polymorphisms in the BMP2 gene and bone mass, fracture, and quantitative ultrasound (QUS) measures at different stages of skeletal development. Study subjects were participants of two population-based cohorts of Swedish women: the PEAK-25 cohort of young adult women aged 25 years (n = 993) and the OPRA cohort of elderly women aged 75 years (n = 1,001). We analyzed four single-nucleotide polymorphisms (SNPs) across the BMP2 gene including the Ser37Ala SNP previously identified in relation to BMD, QUS of the calcaneus, and, in the elderly women, fracture. BMP2 gene variations were associated with QUS of bone, independent of BMD, but only in the young women. Even after adjusting for confounding factors, SNP rs235754 in the 3' region of the gene was significantly associated with the ultrasound parameters speed of sound (P = 0.003) and stiffness (P = 0.002). The 5' SNP rs235710 showed trends for QUS parameters (P = 0.02-0.07). No association with BMP2 SNPs was observed in either cohort for either BMD or fracture. While further, more extensive genotyping across the gene is recommended, as we may not have captured all information, our preliminary data suggest that variation in BMP2 may play a previously unidentified role in aspects of bone quality, which may be age- and site-dependent.

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

“…BMP2 gene variants have variously been linked to BMD and osteoporotic fracture, and in our cohorts with ultrasound parameters (12). Since adipocytes may be influenced by BMP2, we hypothesised that variation in BMP2 might contribute to the distribution of fat mass and hence indirectly contribute to bone mass.…”

“…The women, all of whom were aged 25 years at inclusion, were randomly selected from the city files. Full details of both cohorts have been reported previously (12,13). All participants gave informed consent and the studies were approved by the Lund University Ethics Committee.…”

“…In the absence of available data on tagging SNPs at that time, SNPs were selected on the following criteria: relative position to the gene, minor allele frequency in Caucasian populations and distance between the polymorphisms. These were (in chromosomal order) rs235710 (10 kb upstream), rs2273073 (Ser37Ala) in exon 2, rs235767 in intron 2 and rs235754 (8 kb downstream) (12).…”

“…A further 3% of all PEAK-25 samples and 4.5% of all OPRA samples underwent additional checks for the Ser37Ala polymorphism, with concurrence of results. Full details of the methodology have been described previously (12).…”

Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes

“…The women are all 25 years old and randomly selected from the Malmö city files between 1999 and 2003. 35 The second cohort consists of 1010 healthy controls from the Malmö OPRA study, all aged 75 years and of Swedish or Northeuropean ancestry, randomly selected from the Malmö city files between 1995 and 1999. 36 Additional information regarding the cohorts is available in Supplementary Table S3.…”