Association between Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor β1 Concentration in Human Plasma.

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 by () mutations and subsequent defects in signaling system. single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-β1 and SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-β1 levels in human blood plasma and rs2118181 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 of rs1059177 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 ( = 0.001). A strong correlation between TGF-β1 levels and SNPs suggests that a single nucleotide substitution in sequence 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 and SNPs 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.