Genome-wide Copy-Number-Variation Study Identified a Susceptibility Gene, UGT2B17, for Osteoporosis

Tie Lin Yang, Xiang Ding Chen, Yan Guo, Shu Feng Lei, Jin Tang Wang, Qi Zhou, Feng Pan, Yuan Chen, Zhi Xin Zhang, Shan Shan Dong, Xiang Hong Xu, Han Yan, Xiaogang Liu, Chuan Qiu, Xue Zhen Zhu, Teng Chen, Meng Li, Hong Zhang, Liang Zhang, Betty M. DreesJames J. Hamilton, Christopher J. Papasian, Robert R. Recker, Xiao Ping Song, Jing Cheng, Hong Wen Deng

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165 Scopus citations


Osteoporosis, a highly heritable disease, is characterized mainly by low bone-mineral density (BMD), poor bone geometry, and/or osteoporotic fractures (OF). Copy-number variation (CNV) has been shown to be associated with complex human diseases. The contribution of CNV to osteoporosis has not been determined yet. We conducted case-control genome-wide CNV analyses, using the Affymetrix 500K Array Set, in 700 elderly Chinese individuals comprising 350 cases with homogeneous hip OF and 350 matched controls. We constructed a genomic map containing 727 CNV regions in Chinese individuals. We found that CNV 4q13.2 was strongly associated with OF (p = 2.0 × 10-4, Bonferroni-corrected p = 0.02, odds ratio = 1.73). Validation experiments using PCR and electrophoresis, as well as real-time PCR, further identified a deletion variant of UGT2B17 in CNV 4q13.2. Importantly, the association between CNV of UGT2B17 and OF was successfully replicated in an independent Chinese sample containing 399 cases with hip OF and 400 controls. We further examined this CNV's relevance to major risk factors for OF (i.e., hip BMD and femoral-neck bone geometry) in both Chinese (689 subjects) and white (1000 subjects) samples and found consistently significant results (p = 5.0 × 10-4 -0.021). Because UGT2B17 encodes an enzyme catabolizing steroid hormones, we measured the concentrations of serum testosterone and estradiol for 236 young Chinese males and assessed their UGT2B17 copy number. Subjects without UGT2B17 had significantly higher concentrations of testosterone and estradiol. Our findings suggest the important contribution of CNV of UGT2B17 to the pathogenesis of osteoporosis.

Original languageEnglish (US)
Pages (from-to)663-674
Number of pages12
JournalAmerican journal of human genetics
Issue number6
StatePublished - Dec 12 2008

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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