11Ala and A Alleles of RUNX2 associated with BMD in Scottish women; interaction of RUNX2 alleles with weight.

Abstract

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. To further decipher the role of the RUNX2 A allele we genotyped 992 women from a Scottish cohort. The A allele was associated with higher femoral neck (FN) BMD (p=0.035) within a postmenopausal subgroup of the population (n=312). When the postmenopausal group was segregated into thin/normal (BMI ≤ 25 kg/m2) and overweight /obese (BMI > 25 kg/m2), within the BMI > 25 kg/m2 group (n=140) the RUNX2 A allele showed a stronger effect on FN BMD, with the A allele accounting for 6.8% of the variance of FN BMD. Significant differences in FN BMD were detected in both A allele carriers (GA and AA genotypes) and non-A allele carriers (GG genotype) when comparing thin/normal women to overweight/obese women. The 11Ala RUNX2 deletion allele was significantly associated with decreased lumbar spine (LS) BMD (p=0.018) within the BMI > 25 kg/m2 group (n=546) of the whole group. The 11Ala allele was significantly associated with increased levels of pyridinoline (p=0.014) and deoxypyridinoline (p=0.038) in the HRT treated subgroup of the population (n=492). Glutamine variants and an alanine insertion were identified within the group. These data suggest that the RUNX2 11Ala and A alleles exert differing affects on BMD showing preference for different skeletal sites.