Association of a high mobility group gene (HMGA2) variant with bone mineral density
| Autor: | Yingze Zhang, Jane A. Cauley, Clareann H. Bunker, Allison L. Kuipers, Alan L. Patrick, Victor W. Wheeler, Eric S. Orwoll, Yanxia Chu, Cara S. Nestlerode, Andrew R. Hoffman, Joseph M. Zmuda |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism Osteoporosis Black People Biology Bone and Bones White People Article Cell Line HMGA2 Bone Density Internal medicine Epidemiology medicine Humans Protein Isoforms RNA Messenger Quantitative computed tomography Genotyping Aged Aged 80 and over Genetics Bone mineral Osteoblasts Anthropometry medicine.diagnostic_test HMGA2 Protein Middle Aged medicine.disease Minor allele frequency Endocrinology High-mobility group Caribbean Region Gene Expression Regulation biology.protein |
| Zdroj: | Bone. 45:295-300 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/j.bone.2009.04.197 |
| Popis: | 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 agedor = 40 years and 1548 Caucasian American men agedor = 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 (p0.0001). 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. |
| Databáze: | OpenAIRE |
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