Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People's Republic of China.
PLoS One. 2011;6(7):e22035. doi: 10.1371/journal.pone.0022035. Epub 2011 Jul 15.
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.
骨质疏松性髋部骨折（HF）是一个严重的全球性公共健康问题，与高发病率和死亡率相关。髋骨大小（BS）已被确定为 HF 的关键可测量风险因素之一，独立于骨密度（BMD）。髋 BS 高度受遗传决定，但 BS 变异的遗传因素仍未得到明确界定。在这里，我们使用 Affymetrix GeneChip Human Mapping SNP 6.0 Array 对 1627 名中国汉族受试者的髋 BS 进行了首次全基因组拷贝数变异（CNV）关联分析，并在 2286 名无关的美国白种人样本中进行了后续重复研究。我们发现，位于染色体 2q12.2 上的一个拷贝数多态性（CNP267）在初始中国和重复白种人样本中均与髋 BS 显著相关，p 值分别为 4.73E-03 和 5.66E-03。CNP267 下游检测到一个重要的候选基因，四个半 LIM 结构域 2（FHL2），它在骨代谢中通过与几种骨形成调节剂（如胰岛素样生长因子结合蛋白 5（IGFBP-5）和雄激素受体（AR））结合发挥重要作用。我们的研究结果表明，CNP267 区域可能与髋 BS 相关，这可能会影响下游的 FHL2 基因。
