title: Implication of VEGFR2 in systemic lupus erythematosus: a combined genetic and structural biological approach.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Medical School of Crete, Heraklion, Greece. vazsg@med.uoc.gr
authors.forename: Vassilis M
authors.initials: VM
authors.lastname: Vazgiourakis
authors.forename: Maria I
authors.initials: MI
authors.lastname: Zervou
authors.forename: Elias
authors.initials: E
authors.lastname: Eliopoulos
authors.forename: Shruti
authors.initials: S
authors.lastname: Sharma
authors.forename: Prodromos
authors.initials: P
authors.lastname: Sidiropoulos
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Franek
authors.forename: Effie
authors.initials: E
authors.lastname: Myrthianou
authors.forename: Maria
authors.initials: M
authors.lastname: Melissourgaki
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: George N
authors.initials: GN
authors.lastname: Goulielmos
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006115:Greece; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D016017:Odds Ratio; D010641:Phenotype; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D012307:Risk Factors; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2