Copy Number Variation in CNP267 Region May Be Associated with Hip Bone Size

• Published in: PloS one Vol. 6; no. 7; p. e22035
• Main Authors: Liu, Shan-Lin, Lei, Shu-Feng, Yang, Fang, Li, Xi, Liu, Rong, Nie, Shan, Liu, Xiao-Gang, Yang, Tie-Lin, Guo, Yan, Deng, Fei-Yan, Tian, Qing, Li, Jian, Liu, Yao-Zhong, Liu, Yong-Jun, Shen, Hui, Deng, Hong-Wen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.07.2011; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Androgen receptors; Asian Continental Ancestry Group - genetics; Association analysis; Biocompatibility; Bioinformatics; Biology; Biomedical materials; Bone and Bones - anatomy & histology; Bone density; Bone growth; Bone mineral density; Bone turnover; Chromosome 2; Chromosomes, Human, Pair 2 - genetics; Copy number; Cultural differences; Developmental biology; DNA Copy Number Variations - genetics; Education; Ethnic Groups - genetics; Ethnicity; European Continental Ancestry Group - genetics; Female; FHL2 protein; Fractures; Gene expression; Gene mapping; Genes; Genetic Association Studies; Genetic diversity; Genetic factors; Genetics; Genomes; Genomics; Health aspects; Hip; Hip - anatomy & histology; Humans; Insulin; Insulin-like growth factor-binding protein 5; Laboratories; Life sciences; Male; Males; Medicine; Metabolism; Morbidity; Mortality; Mutation; Organ Size - genetics; Osteogenesis; Osteoporosis; Parkinson's disease; Physiological aspects; Polymorphism; Protein binding; Proteins; Public health; Risk analysis; Risk factors; Single-nucleotide polymorphism; Trauma; White people; Louisiana; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022035

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.