Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.

Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.
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DOI:
10.1002/mgg3.1391
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发表时间:
2020-09
影响因子:
2
通讯作者:
Pereira RMR
Pereira RMR
中科院分区:
医学4区
文献类型:
--
作者:
Jales Neto LH;Wicik Z;Torres GHF;Takayama L;Caparbo VF;Lopes NHM;Pereira AC;Pereira RMR

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椎体骨折是骨质疏松症最常见的临床表现,死亡率高。个人/熟悉的骨折史会增加骨折的风险。本研究的目的是确定可能的分子标记物与老年妇女的艾滋病VF从社区。使用来自基于人群的调查(圣保罗老龄化与健康[SPAH]研究)的240名受试者的全血样品,使用Affyphase HTA 2微阵列进行转录组学分析。仅对通过密度测定诊断为骨质疏松症的老年女性进行分析,并将其分为两组:VF:骨质疏松症和VF的女性与无椎骨骨折(NVF):骨质疏松症和NVF的女性。他们的年龄、慢性疾病、药物使用和骨密度(BMD)相匹配。将针对年龄调整的逻辑回归模型应用于转录组数据分析。使用基于SYBR绿色的定量聚合酶链反应(qPCR)验证微阵列实验中获得的最显著表达变化。微阵列分析鉴定了142个差异表达基因(DEG,p <0.01),将VF组与NVF组进行比较,其中57个上调,85个下调。具有最大表达差异的DEG是γ 2-促突触蛋白(SNTG 2)(β = 31.88,p = .005)。通过qPCR的验证证实VF组中的突触营养蛋白(SNTG 2,倍数变化= 2.79,p = .009)、TRAF 3相互作用蛋白2(TRAF 3 IP 2,倍数变化= 2.79,p = .020)和整联蛋白亚基α 6(ITGA 6,倍数变化= 2.86,p = .038)的表达增加。我们的数据确定并验证了SNTG 2(608715)、TRAF 3 IP 2(607043)和ITGA 6(147556)与老年女性的退行性VF的相关性,与BMD无关。这些结果表明,这些转录本具有潜在的临床意义,可能有助于解释脊椎骨折的分子机制和生物学功能。我们的数据确定并验证了SNTG 2、TRAF 3 IP 2和ITGA 6与老年女性骨质疏松性椎体骨折(VF)的相关性,与骨密度无关。这些结果表明,这些转录本具有潜在的临床意义,可能有助于解释VF的分子机制和生物学功能。
Vertebral fractures (VFs) are the most common clinical manifestation of osteoporosis associated with high morbimortality. A personal/familiar history of fractures increases the risk of fractures. The purpose of this study is to identify possible molecular markers associated with osteoporotic VFs in elderly women from community. Transcriptomic analysis using Affymetrix HTA2 microarray was performed using whole blood samples of 240 subjects from a population‐based survey (Sao Paulo Ageing & Health [SPAH] study). Only elderly women with osteoporosis diagnosis by densitometry were analyzed, and divided in two groups: VF: women with osteoporosis and VFs versus no vertebral fracture (NVF): women with osteoporosis and NVFs. They were matched for age, chronic disease, medication use, and bone mineral density (BMD). The logistic regression model adjusted for age was applied for transcriptome data analysis. SYBR green‐based quantitative polymerase chain reaction (qPCR) was used to validate the most significant expression changes obtained in the microarray experiment. Microarray analysis identified 142 differentially expressed genes (DEGs, p < .01), 57 upregulated and 85 downregulated, compared VF versus NVF groups. The DEG with the greatest expression difference was the Gamma2‐Syntrophin (SNTG2) (β = 31.88, p = .005). Validation by qPCR confirmed increased expression in VF group of Syntrophin (SNTG2, fold change = 2.79, p = .009), TRAF3 Interacting Protein2 (TRAF3IP2, fold change = 2.79, p = .020), and Integrin Subunit Alpha 6 (ITGA6, fold change = 2.86, p = .038). Our data identified and validated the association of SNTG2 (608715), TRAF3IP2 (607043), and ITGA6 (147556) with osteoporotic VF in elderly women, independently of BMD. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of vertebral fracture. Our data identified and validated the association of SNTG2, TRAF3IP2, and ITGA6 with osteoporotic vertebral fracture (VF) in elderly women, independently of bone mineral density. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of VF.
DOI: 10.1359/jbmr.061113
发表时间: 2007-03-01
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