Association of a high mobility group gene (HMGA2) variant with bone mineral density

Allison Kuipers, Yingze Zhang, Jane A. Cauley, Cara S. Nestlerode, Yanxia Chu, Clareann H. Bunker, Alan L. Patrick, Victor W. Wheeler, Andrew R. Hoffman, Eric Orwoll, Joseph M. Zmuda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

High mobility group (HMG) proteins regulate chromatin architecture and gene expression. Constitutional rearrangement of an HMG family member, HMGA2, in an 8-year old boy resulted in extreme overgrowth and advanced bone development. Moreover, a recent genome-wide association study documented an association between a variant in the 3′ untranslated region of HMGA2 (rs1042725) and height in otherwise healthy individuals. We attempted to extend these findings by testing if this HMGA2 polymorphism is associated with other skeletal measures in two large population cohorts of diverse race/ethnicity. Genotyping was completed in 1680 Afro-Caribbean men aged ≥ 40 years and 1548 Caucasian American men aged ≥ 69 years. Bone mineral density (BMD) was assessed with peripheral quantitative computed tomography. The minor allele frequency of rs1042725 was 32% among Afro-Caribbeans and 48% among Caucasians (p <0.0001). No association was observed with height in either study cohort. However, presence of the minor allele of this SNP was associated with decreased tibia trabecular volumetric BMD in both populations (p = 0.007 Afro-Caribbean; p = 0.0007 Caucasian). Real-time quantitative RT-PCR and Western blot analysis demonstrated HMGA2 mRNA and protein expression in the human fetal osteoblast cell line, hFOB. Our analyses suggest a novel association between a common genetic variant in HMGA2 and trabecular BMD in ethnically diverse older men. Additional research is needed to better understand the role of HMGA2 in the regulation of bone metabolism.

Original languageEnglish (US)
Pages (from-to)295-300
Number of pages6
JournalBone
Volume45
Issue number2
DOIs
StatePublished - Aug 2009

Fingerprint

Bone Density
HMGA2 Protein
Genes
High Mobility Group Proteins
Genome-Wide Association Study
Bone Development
3' Untranslated Regions
Osteoblasts
Tibia
Gene Frequency
Population
Chromatin
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Cohort Studies
Western Blotting
Alleles
Tomography
Gene Expression
Bone and Bones

Keywords

  • BMD
  • Genetics
  • HMGA2
  • Men
  • Osteoporosis
  • Race

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Kuipers, A., Zhang, Y., Cauley, J. A., Nestlerode, C. S., Chu, Y., Bunker, C. H., ... Zmuda, J. M. (2009). Association of a high mobility group gene (HMGA2) variant with bone mineral density. Bone, 45(2), 295-300. https://doi.org/10.1016/j.bone.2009.04.197

Association of a high mobility group gene (HMGA2) variant with bone mineral density. / Kuipers, Allison; Zhang, Yingze; Cauley, Jane A.; Nestlerode, Cara S.; Chu, Yanxia; Bunker, Clareann H.; Patrick, Alan L.; Wheeler, Victor W.; Hoffman, Andrew R.; Orwoll, Eric; Zmuda, Joseph M.

In: Bone, Vol. 45, No. 2, 08.2009, p. 295-300.

Research output: Contribution to journalArticle

Kuipers, A, Zhang, Y, Cauley, JA, Nestlerode, CS, Chu, Y, Bunker, CH, Patrick, AL, Wheeler, VW, Hoffman, AR, Orwoll, E & Zmuda, JM 2009, 'Association of a high mobility group gene (HMGA2) variant with bone mineral density', Bone, vol. 45, no. 2, pp. 295-300. https://doi.org/10.1016/j.bone.2009.04.197
Kuipers A, Zhang Y, Cauley JA, Nestlerode CS, Chu Y, Bunker CH et al. Association of a high mobility group gene (HMGA2) variant with bone mineral density. Bone. 2009 Aug;45(2):295-300. https://doi.org/10.1016/j.bone.2009.04.197
Kuipers, Allison ; Zhang, Yingze ; Cauley, Jane A. ; Nestlerode, Cara S. ; Chu, Yanxia ; Bunker, Clareann H. ; Patrick, Alan L. ; Wheeler, Victor W. ; Hoffman, Andrew R. ; Orwoll, Eric ; Zmuda, Joseph M. / Association of a high mobility group gene (HMGA2) variant with bone mineral density. In: Bone. 2009 ; Vol. 45, No. 2. pp. 295-300.
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