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Bone. 2004 Jun;34(6):1029-36.

RUNX2 alleles associated with BMD in Scottish women; interaction of RUNX2 alleles with menopausal status and body mass index.

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School of Health Science, Griffith University Gold Coast Campus, 4215 Queensland, Australia.


Bone mineral density (BMD) is influenced by both environmental and genetic factors. We previously reported the association of the RUNX2 A allele with increased bone mineral density (BMD) and protection against a common form of osteoporotic fracture within a Geelong population. We genotyped 991 women from a Scottish cohort to decipher the role of RUNX2 alleles in regulating BMD. The alleles of RUNX2 within the glutamine-alanine repeat were determined by MspA1I restriction digest. Allele frequencies estimated from Scottish cohort were G allele, 0.87 +/- 0.01; A allele, 0.08 +/- 0.01; and 11Ala alanine deletion allele, 0.05 +/- 0.01. Analysis of covariance (ANCOVA) was used to adjust for the covariates weight and age for BMD at the femoral neck (FN). The A allele was associated with higher FN BMD (P = 0.035) within a postmenopausal subgroup of the population (n = 312). The effect of RUNX2 A alleles increased with increasing weight; A alleles were associated with FN BMD in those above the median BMI (BMI > 25), while no association was observed in thin/normal (BMI </= 25) postmenopausal women. Glutamine variants and an alanine insertion were identified within the group. These data suggest that the RUNX2 alleles are associated with BMD in a menopause- and weight-dependent manner.

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