Hip geometry variation is associated with bone mineralization pathway gene variants: The Framingham study

Ching Lung Cheung, Gregory Livshits, Yanhua Zhou, James B. Meigs, Jarred B. McAteer, Jose C. Florez, L. Adrienne Cupples, Serkalem Demissie, Douglas P. Kiel, David Karasik

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Mineralization of bone matrix is an important process in bone formation; thus defects in mineralization have been implicated in bone mineral density (BMD) and bone structure alterations. Three central regulators of phosphate balance, ALPL, ANKH, and ENPP1, are central in the matrix mineralization process; therefore, the genes encoding them are considered important candidates genes for BMD and bone geometry. To test for an association between these three candidate genes and BMD and bone geometry traits, 124 informative single-nucleotide polymorphisms (SNPs) were selected and genotyped in 1513 unrelated subjects from the Framingham offspring cohort. Initial results showed that SNP rs1974201 in the gene ENPP1 was a susceptibility variant associated with several hip geometric indices, with the strongest p value of 3.8×10 -7 being observed for femoral neck width. A few modest associations were observed between SNPs in or near ALPL and several bone traits, but no association was observed with ANKH. The association signals observed for SNPs around rs1974201 were attenuated after conditional analysis on rs1974201. Transcription factor binding-site prediction revealed that the HOXA7 binding site was present in the reference sequence with the major allele, whereas this potential binding site is lost in the sequence with the minor allele of rs1974201. In conclusion, we found evidence for association of bone geometry variation with an SNP in ENPP1, a gene in the mineralization pathway. The alteration of a binding site of the deregulator of extracellular matrix HOXA7 warrants further investigation.

Original languageEnglish
Pages (from-to)1564-1571
Number of pages8
JournalJournal of Bone and Mineral Research
Issue number7
StatePublished - Jul 2010
Externally publishedYes


  • ALPL
  • ANKH
  • Association
  • Bone geometry
  • Bone mineral density
  • ENPP1
  • Mineralization


Dive into the research topics of 'Hip geometry variation is associated with bone mineralization pathway gene variants: The Framingham study'. Together they form a unique fingerprint.

Cite this