title: Association betweenFibrillin1Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor β1 Concentration in Human Plasma.
abstract: Transforming growth factor (TGF)-β1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF-β1 levels are linked to Marfan syndrome (MFS) caused byfibrillin1(FBN1) mutations and subsequent defects in signaling system.FBN1single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-β1 andFBN1SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-β1 levels in human blood plasma andFBN1rs2118181 and rs1059177 in 269 individuals. The results showed a quantitative dependence of SNP genotype and TGF-β1 concentration. Presence of a single rs2118181 minor allele (G) increased the amount of TGF-β1 by roughly 1 ng/mL. Two copies ofFBN1rs1059177 minor allele (G) were required to have an additive effect on TGF-β1 levels. We found higher TGF-β1 concentrations in men compared with women (p= 0.001). A strong correlation between TGF-β1 levels andFBN1SNPs suggests that a single nucleotide substitution inFBN1sequence might reduce bioavailability or binding properties of fibrillin-1 and have an effect on TGF-β1 activation and cytokine concentration in blood plasma. By establishing the relationship between TGF-β1 andFBN1SNPs rs2118181 and rs1059177, we provide evidence that their combination might be used as molecular biomarkers to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection.
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Ramune
authors: R
authors: Sepetiene
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Vaiva
authors: V
authors: Patamsyte
authors: Department of Cardiac, Thoracic and Vascular Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Giedrius
authors: G
authors: Zukovas
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Giedre
authors: G
authors: Jariene
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Zita
authors: Z
authors: Stanioniene
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.|Department of Cardiac, Thoracic and Vascular Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Rimantas
authors: R
authors: Benetis
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Abdonas
authors: A
authors: Tamosiunas
authors: Institute of Cardiology of the Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Vaiva
authors: V
authors: Lesauskaite