Investigation of TGFßR2 SNP rs4522809, Osteopontin, TGF ß1 and their association with dilatative pathology of ascending thoracic aorta.

BACKGROUND: Dilatative pathology of the ascending thoracic aorta (DPATA) is characterized by the aortic wall expansion more than 1.5 and could be accompanied by aortic wall rupture. Mutations of TGFBR2 gene demonstrated an association with syndromic DPATA and altered pathway of transforming growth factor beta (TGF-ß). Elevated TGF-ß1 level has been found in blood samples in DPATA group. Moreover, elevated osteopontin (OPN) level was associated with mutations of TGFBR2 gene. Based on recently published findings, we aimed to evaluate genotyping results of TGFBR2 rs4522809 and the association with circulating OPN and TGF-ß1 concentrations within DPATA patients. METHODS AND FINDINGS: TGFBR2 SNP genotyping assay was performed by quantitative real-time PCR, TGF-ß1 and OPN concentrations were measured using enzyme-linked immunosorbent assay. Genotyping results showed G allele to be associated with DPATA (p = .01), the presence of G allele significantly increased the possibility of DPATA by 1.67 times (OR = 1.67, 95%, CI = 1.12-2.47). TGF-ß1 concentration was significantly higher in DPATA subjects compared with Reference group (p = 0,001). Finally, we found moderate inverse correlation (r = -0,524) between circulating TGF-ß1 and OPN levels within DPATA subjects (p = 0,002), as increasing levels of TGF-ß1 cytokine significantly decrease concentration of OPN. CONCLUSIONS: This is the first report on the association between previously defined TGFßR2 SNP rs4522809 linked with dilatation of ascending thoracic aorta. Also, for the first time we report the inversed correlation between circulating TGF-ß1 and OPN concentrations in DPATA subjects indicating the possible biomarkers for DPATA.