Association of a high mobility group gene (HMGA2) variant with bone mineral density.
Association of a high mobility group gene (HMGA2) variant with bone mineral density.
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DOI：
10.1016/j.bone.2009.04.197
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发表时间：
2009-08
期刊：
影响因子：
4.1
通讯作者：
Zmuda, Joseph M.
中科院分区：
文献类型：
--
作者：
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 S.;Zmuda, Joseph M.
高迁移率族（HMG）蛋白调节染色质结构和基因表达。HMG家族成员HMGA 2在一名8岁男孩中的宪法重排导致极度过度生长和骨发育。此外，最近的一项全基因组关联研究记录了HMGA 2 3′非翻译区（rs 1042725）的变异与其他健康个体的身高之间的关联。我们试图通过在两个不同种族/民族的大人群队列中检测HMGA 2多态性是否与其他骨骼指标相关来扩展这些发现。在1，680名年龄≥40岁的非洲裔加勒比男性和1，548名年龄≥69岁的白人美国男性中完成了基因分型。采用外周定量计算机断层扫描评估骨密度（BMD）。rs 1042725的次要等位基因频率在非洲-加勒比人中为32%，在高加索人中为48%（p<0.0001）。在两个研究队列中均未观察到与身高相关。然而，该SNP的次要等位基因的存在与两个人群中胫骨骨小梁体积BMD的降低相关（p=0.007非洲-加勒比人; p=0.0007高加索人）。真实的时间定量RT-PCR和Western blot分析证实HMGA 2 mRNA和蛋白在人胎儿成骨细胞系hFOB中表达。我们的分析表明，在不同种族的老年男性中，HMGA 2的一种常见遗传变异与骨小梁BMD之间存在一种新的关联。需要更多的研究来更好地了解HMGA 2在骨代谢调节中的作用。
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 1,680 Afro-Caribbean men aged ≥40 years and 1,548 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.
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影响因子：
2.2
作者：
Orwoll, E;Blank, JB;Stone, K
通讯作者：
Stone, K
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Sanna, Serena;Jackson, Anne U.;Mohlke, Karen L.
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Mohlke, Karen L.
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作者：
Thuault, Sylvie;Valcourt, Ulrich;Petersen, Maj;Manfioletti, Guidalberto;Heldin, Carl-Henrik;Moustakas, Aristidis
通讯作者：
Moustakas, Aristidis
影响因子：
4
作者：
Hill, D. D.;Cauley, J. A.;Zmuda, J. M.
通讯作者：
Zmuda, J. M.