Association between Secreted Phosphoprotein-1 (SPP1) Polymorphisms and Low Bone Mineral Density in Women

BACKGROUND: A recent meta-analysis found that secreted phosphoprotein-1 (SPP1) can predict the risk of both osteoporosis and fracture. No study has explored the association of SPP1 haplotype-tagging single nucleotide polymorphisms (htSNPs) and haplotypes with bone mineral density (BMD). METHODS: This is a cross-sectional study. A total of 1,313 healthy Taiwanese women aged 40 to 55 years were recruited from MJ Health Management Institute from 2009 to 2010. BMD was dichotomized into high and low BMD groups. Three common (allele frequency ≥5%) htSNPs were selected to examine the association between sequence variants of SPP1 and BMD. RESULTS: Homozygosity for the T allele of rs4754 were protective from low BMD [TT vs. CC: adjusted OR (AOR) = 0.58, 95% confidence interval (CI) = 0.83–0.89]. A protective effect was also found for women carrying 2 copies of Hap3 TCT (AOR = 0.57, 95% CI = 0.34–0.95). Menopausal status marginally interacted with SPP1 rs6839524 on BMD (p = 0.049). Postmenopausal women carrying variant rs6839524 (GG+GC vs. CC: AOR = 2.35, 95% CI = 1.06–5.20) or Hap1 TGC (AOR = 2.36, 95% CI = 1.06–5.24) were associated with 2.4-fold risk of low BMD. For women with low BMI (<18.5 kg/m(2)), variant rs6839524 (AOR = 7.64) and Hap1 (AOR = 6.42) were associated with increased risk of low BMD. These findings did not reach statistical significance after correction for multiple tests. CONCLUSIONS: SPP1 htSNP protected against low BMD in middle-aged women. SPP1 genetic markers may be important for the prediction of osteoporosis at an early age.