PLoS ONE (Jan 2011)

Copy number variation in CNP267 region may be associated with hip bone size.

  • Shan-Lin Liu,
  • Shu-Feng Lei,
  • Fang Yang,
  • Xi Li,
  • Rong Liu,
  • Shan Nie,
  • Xiao-Gang Liu,
  • Tie-Lin Yang,
  • Yan Guo,
  • Fei-Yan Deng,
  • Qing Tian,
  • Jian Li,
  • Yao-Zhong Liu,
  • Yong-Jun Liu,
  • Hui Shen,
  • Hong-Wen Deng

DOI
https://doi.org/10.1371/journal.pone.0022035
Journal volume & issue
Vol. 6, no. 7
p. e22035

Abstract

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Osteoporotic hip fracture (HF) is a serious global public health problem associated with high morbidity and mortality. Hip bone size (BS) has been identified as one of key measurable risk factors for HF, independent of bone mineral density (BMD). Hip BS is highly genetically determined, but genetic factors underlying BS variation are still poorly defined. Here, we performed an initial genome-wide copy number variation (CNV) association analysis for hip BS in 1,627 Chinese Han subjects using Affymetrix GeneChip Human Mapping SNP 6.0 Array and a follow-up replicate study in 2,286 unrelated US Caucasians sample. We found that a copy number polymorphism (CNP267) located at chromosome 2q12.2 was significantly associated with hip BS in both initial Chinese and replicate Caucasian samples with p values of 4.73E-03 and 5.66E-03, respectively. An important candidate gene, four and a half LIM domains 2 (FHL2), was detected at the downstream of CNP267, which plays important roles in bone metabolism by binding to several bone formation regulator, such as insulin-like growth factor-binding protein 5 (IGFBP-5) and androgen receptor (AR). Our findings suggest that CNP267 region may be associated with hip BS which might influence the FHL2 gene downstream.