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

Author(s)

Jales Neto, Levi H. ; Wicik, Zofia ; Torres, Georgea H. F. ; Takayama, Liliam ; Caparbo, Valeria F. ; Lopes, Neuza H. M. ; Pereira, Alexandre C. ; Pereira, Rosa M. R.

• Document type: Journal article
• Source: MOLECULAR GENETICS & GENOMIC MEDICINE; v. 8, n. 9, p. 12-pg., 2020-06-30.

Abstract

Background: 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. Methods: Transcriptomic analysis using Affymetrix HTA2 microarray was performed using whole blood samples of 240 subjects from a population-based survey (Sao Paulo Ageing & Health [SPAR] 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. Results: 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) (beta = 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, told change = 2.79, p = .020), and Integrin Subunit Alpha 6 (ITGA6, fold change = 2.86, p = .038). Conclusion: 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. (AU)

• FAPESP's process: 16/00006-7 - Evaluation of bone metabolism parameters by HR-pQCT and histomorphometry in rheumatoid arthritis and juvenile idiopathic arthritis patients: association with clinical and genetic variables
• Grantee: Eduardo Ferreira Borba Neto
• Support Opportunities: Research Projects - Thematic Grants