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Molecular Medicine

, Volume 21, Issue 1, pp 735–738 | Cite as

Association between Fibrillin1 Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor β1 Concentration in Human Plasma

  • Ramune Sepetiene
  • Vaiva Patamsyte
  • Giedrius Zukovas
  • Giedre Jariene
  • Zita Stanioniene
  • Rimantas Benetis
  • Abdonas Tamosiunas
  • Vaiva Lesauskaite
Research Article

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 by fibrillin1 (FBN1) mutations and subsequent defects in signaling system. FBN1 single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-β1 and FBN1 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 FBN1 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 FBN1 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 (p = 0.001). A strong correlation between TGF-β1 levels and FBN1 SNPs suggests that a single nucleotide substitution in FBN1 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 FBN1 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.

Notes

Acknowledgments

Financial support for the study was provided by the Research Council of Lithuania for National Research Programme “Chronic Noncommunicable Diseases” (Agreement No LIG 05/2012).

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Authors and Affiliations

  • Ramune Sepetiene
    • 1
  • Vaiva Patamsyte
    • 1
  • Giedrius Zukovas
    • 2
  • Giedre Jariene
    • 1
  • Zita Stanioniene
    • 1
  • Rimantas Benetis
    • 1
    • 2
  • Abdonas Tamosiunas
    • 1
  • Vaiva Lesauskaite
    • 1
  1. 1.Institute of Cardiology of the Medical AcademyLithuanian University of Health SciencesKaunasLithuania
  2. 2.Department of Cardiac, Thoracic and Vascular SurgeryLithuanian University of Health SciencesKaunasLithuania

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