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/m2), 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.
Department of Geriatrics and Gerontology, National Taiwan University Hospital, No. 1, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, No. 7, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Jen-Hau
JH
Chen
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Yen-Ching
YC
Chen
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Chien-Lin
CL
Mao
Institute of Statistical Science, Academia Sinica, Nankang, Taipei, Taiwan.
Jeng-Min
JM
Chiou
MJ Health Management Institution, 12F., No. 413, Section 4, Taipei, Taiwan.
Chwen Keng
CK
Tsao
Department of Geriatrics and Gerontology, National Taiwan University Hospital, No. 1, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, No. 7, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Taipei, Taiwan.
Keh-Sung
KS
Tsai
D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011795:Surveys and Questionnaires; D013624:Taiwan
C506895:SPP1 protein, human; D053495:Osteopontin