Implication of VEGFR2 in systemic lupus erythematosus: A combined genetic and structural biological approach

Vassillis M. Vazgiourakis, Maria I. Zervou, Elias Eliopoulos, Shruti Sharma, Prodromos Sidiropoulos, Beverly S. Franek, Effie Myrthianou, Maria Melissourgaki, Timothy B. Niewold, Dimitrios T. Boumpas, George N. Goulielmos

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Objectives: VEGFR2 gene polymorphisms have already been correlated with vascular diseases such as coronary heart disease (CHD) and may influence endothelial integrity, repair and function. In view of the premature atherosclerosis observed in SLE, we sought to clarify the structural/functional consequences of two common single nucleotide polymorphisms (SNPs) of VEGFR2 in SLE and determine whether they are associated with risk of SLE by influencing endothelial cells. Methods: Three-dimensional (3D) homology modelling was applied for the localisation of the V297I and the Q472H polymorphisms. Genotyping of the V297I (rs2305948) and Q472H (rs1870377) SNPs was done through Taqman technology in 250 SLE patients and 241 healthy controls from a Greek population (Cretan). The replication sample set for the rs1870377 SNP consisted of 253, 184 and 77 patients with SLE and 301, 118 and 11 ethnically-matched controls of African-American, European-American and Hispanic-American origin, respectively. Results: Modelling revealed that the V297I polymorphism may affect the efficiency of trans-autophosphorylation and cell signalling, while Q472H affects homotypic contacts of membrane proximal Ig-like domains. No significant allelic and genotypic association was observed for both the SNPs with risk of SLE. Conclusion: Although structural data suggest that both VEGFR2 SNPs may contribute to SLE pathogenesis by impairing VEGF signalling, none of the SNPs analysed was associated with increased susceptibility to SLE. However, they still may be relevant to the vascular damage/atherosclerosis in SLE.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalClinical and experimental rheumatology
Volume31
Issue number1
StatePublished - Jan 1 2013

Keywords

  • Association study
  • Gene polymorphisms
  • Systemic lupus erythematosus
  • Three-Dimensional (3d) Model

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Vazgiourakis, V. M., Zervou, M. I., Eliopoulos, E., Sharma, S., Sidiropoulos, P., Franek, B. S., Myrthianou, E., Melissourgaki, M., Niewold, T. B., Boumpas, D. T., & Goulielmos, G. N. (2013). Implication of VEGFR2 in systemic lupus erythematosus: A combined genetic and structural biological approach. Clinical and experimental rheumatology, 31(1), 97-102.