Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women.
BACKGROUND
Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations.


METHODS
To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2-L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18-61) and 1,291 pre-menopausal women (age 20-50). SNP genotypes/haplotypes were tested for population-based association with BMD using analysis of variance.


RESULTS
None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019-0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons.


CONCLUSIONS
These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.
Ichikawa
S
S
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Johnson
M L
ML
Koller
D L
DL
Lai
D
D
Xuei
X
X
Edenberg
H J
HJ
Hui
S L
SL
Foroud
T M
TM
Peacock
M
M
Econs
M J
MJ
D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014481:United States; D044465:White People
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta