Osteoporosis International

, Volume 16, Issue 12, pp 1519–1524

The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women

Authors

  • Hong-yan Zhao
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
  • Jian-min Liu
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
  • Yong-ju Zhao
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
  • Lian-zhen Zhang
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
  • Li-hao Sun
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
  • Man-yin Xu
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
  • A. G. Uitterlinden
    • Genetic Laboratory, Department of Internal MedicineErasmus MC
  • Jia-lun Chen
    • Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Institute of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Second Medical University
Original Article

DOI: 10.1007/s00198-005-1865-9

Cite this article as:
Zhao, H., Liu, J., Ning, G. et al. Osteoporos Int (2005) 16: 1519. doi:10.1007/s00198-005-1865-9

Abstract

The objective was to identify single nucleotide polymorphisms (SNPs) in exons of the osteoprotegerin gene and to analyze the relationship between the SNPs and bone mineral density in postmenopausal women. We used polymerase chain reaction (PCR) and direct sequencing methods to identify SNPs and genotypes in 205 postmenopausal women. BMD at the lumbar spine (L2–4) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry (DEXA). Serum osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL) and urinary N-telopeptide of type I collagen (NTx) were also measured. In exon 1 of the OPG gene, we found the Lys3Asn SNP. In 205 postmenopausal women, the Asn-allele frequency was 26.0%, and the distribution of Lys3Asn genotypes was Lys-Lys 56.6%, Lys-Asn 34.6% and Asn-Asn 8.8%, respectively. BMD at the lumbar spine (L2–4) of the Asn-Asn genotype was significantly higher (9.5–12.6%) than Lys-Asn and Lys-Lys genotypes ( P =0.012), with evidence for an allele dose effect ( P =0.008). Results remained similar after adjustment for age and body mass index. The Lys3Asn polymorphism of the OPG gene alone accounted for 7.7% of the variance of the L2–4 BMD in a multiple regression model. Logistic regression analysis revealed that the OPG genotype Lys-Lys had a 2.7 times (95% CI: 0.83–9.11) greater risk for osteopenia/osteoporosis than the Asn-Asn genotype. The Lys3Asn polymorphism in the OPG gene is associated with L2–4 BMD in postmenopausal women. The Lys-allele is associated with lower BMD and an increased risk for osteoporosis.

Keywords

Bone mineral densityGeneOsteoprotegerinSingle nucleotide polymorphism

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2005