LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density

J Hum Genet. 2004;49(2):80-86. doi: 10.1007/s10038-003-0111-6. Epub 2004 Jan 15.


Osteoporosis is a multifactorial trait with low bone mineral density (BMD). We report results of an association study between BMD and nine candidate genes ( TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, IFNB1, IFNAR1, FOS and LRP5), as well as of a case-control study of osteoporosis. Samples for the former association study included 481 general Japanese women. Among the nine candidate genes examined, only LRP5 showed a significant association with BMD. We identified a strong linkage disequilibrium (LD) block within LRP5. Of five LPR5 single nucleotide polymorphisms (SNPs) that are located in the LD block, three gave relatively significant results: Women with the C/C genotype at the c.2220C>T SNP site had higher adjusted BMD (AdjBMD) value compared to those with C/T and T/T (p=0.022); and likewise, G/G at IVS17-30G>A and C/C women at c.3989C>T showed higher AdjBMD than those with G/A or A/A (p=0.039) and with C/T or T/T ( p=0.053), respectively. The case-control study in another series of samples consisting of 126 osteoporotic patients and 131 normal controls also gave a significant difference in allele frequency at c.2220C>T (kappa2=6.737, p=0.009). These results suggest that LRP5 is a BMD determinant and also contributes to a risk of osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Bone Density / genetics*
  • Bone Density / physiology
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Humans
  • Japan
  • LDL-Receptor Related Proteins
  • Linkage Disequilibrium
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Osteoporosis / genetics*
  • Polymorphism, Single Nucleotide
  • Receptors, LDL / genetics*
  • Receptors, LDL / physiology*
  • Sequence Analysis, DNA


  • LDL-Receptor Related Proteins
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Receptors, LDL