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 language | English (US) |
|---|---|
| Pages (from-to) | 295-300 |
| Number of pages | 6 |
| Journal | Bone |
| Volume | 45 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2009 |
Fingerprint
Keywords
- BMD
- Genetics
- HMGA2
- Men
- Osteoporosis
- Race
ASJC Scopus subject areas
- Physiology
- Endocrinology, Diabetes and Metabolism
- Histology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Association of a high mobility group gene (HMGA2) variant with bone mineral density
AU - Kuipers, Allison
AU - Zhang, Yingze
AU - Cauley, Jane A.
AU - Nestlerode, Cara S.
AU - Chu, Yanxia
AU - Bunker, Clareann H.
AU - Patrick, Alan L.
AU - Wheeler, Victor W.
AU - Hoffman, Andrew R.
AU - Orwoll, Eric
AU - Zmuda, Joseph M.
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - BMD
KW - Genetics
KW - HMGA2
KW - Men
KW - Osteoporosis
KW - Race
UR - http://www.scopus.com/inward/record.url?scp=67649652034&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649652034&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2009.04.197
DO - 10.1016/j.bone.2009.04.197
M3 - Article
C2 - 19376282
AN - SCOPUS:67649652034
VL - 45
SP - 295
EP - 300
JO - Bone
JF - Bone
SN - 8756-3282
IS - 2
ER -