title: Copy number variation in CNP267 region may be associated with hip bone size.
abstract: 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.
authors.affiliation: 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.
authors.forename: Shan-Lin
authors.initials: SL
authors.lastname: Liu
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Nie
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001842:Bone and Bones / Q000033:anatomy & histology*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006615:Hip / Q000033:anatomy & histology*; D006801:Humans; D008297:Male; D009929:Organ Size / Q000235:genetics; D044465:White People / Q000235:genetics