Article :: Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men

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Original Article

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men

Laura M Yerges¹, Lambertus Klei², Jane A Cauley¹, Kathryn Roeder³, Candace M Kammerer⁴, Kristine E Ensrud⁵, Cara S Nestlerode¹, Cora Lewis⁶, Thomas F Lang⁷, Elizabeth Barrett-Connor⁸, Susan P Moffett¹, Andrew R Hoffman⁹, Robert E Ferrell⁴, Eric S Orwoll¹⁰, Joseph M Zmuda^{1 4 *}, for the Osteoporotic Fractures in Men (MrOS) Study Group

¹Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
²Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
³Statistics, Carnegie Mellon University, Pittsburgh, PA, USA
⁴Genetics, University of Pittsburgh, Pittsburgh, PA, USA
⁵Medicine, University of Minnesota, Minneapolis, MN, USA
⁶University of Alabama at Birmingham, Birmingham, AL, USA
⁷Radiology, University of California-San Francisco, San Francisco, CA, USA
⁸Department of Family and Preventive Medicine, University of California-San Diego, La Jolla, CA, USA
⁹Veterans Affairs, Palo Alto Health Care System and Stanford University, Palo Alto, CA, USA
¹⁰Medicine, Oregon Health & Science University, Portland, OR, USA

email: Joseph M Zmuda (zmudaj@edc.pitt.edu)

^*Correspondence to Joseph M Zmuda, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA.

Keywords

osteoporosis Genetics BMD men qCT

Abstract

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment. © 2010 American Society for Bone and Mineral Research

Received: 22 December 2008; Revised: 10 May 2009; Accepted: 8 July 2009

Digital Object Identifier (DOI)

10.1359/jbmr.090729 About DOI