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

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dc.contributor.author Vazgiourakis, VM en
dc.contributor.author Zervou, MI en
dc.contributor.author Eliopoulos, E en
dc.contributor.author Sharma, S en
dc.contributor.author Sidiropoulos, P en
dc.contributor.author Franek, BS en
dc.contributor.author Myrthianou, E en
dc.contributor.author Melissourgaki, M en
dc.contributor.author Niewold, TB en
dc.contributor.author Boumpas, DT en
dc.contributor.author Goulielmos, GN en
dc.date.accessioned 2014-06-06T06:52:37Z
dc.date.available 2014-06-06T06:52:37Z
dc.date.issued 2013 en
dc.identifier.issn 0392856X en
dc.identifier.uri http://62.217.125.90/xmlui/handle/123456789/6089
dc.relation.uri http://www.scopus.com/inward/record.url?eid=2-s2.0-84874865773&partnerID=40&md5=5d6d6620f07480c969beffaf1e3d01af en
dc.subject Association study en
dc.subject Gene polymorphisms en
dc.subject Systemic lupus erythematosus en
dc.subject Three-Dimensional (3d) Model en
dc.subject.other glutamine en
dc.subject.other histidine en
dc.subject.other immunoglobulin en
dc.subject.other valine en
dc.subject.other vasculotropin receptor 2 en
dc.subject.other adult en
dc.subject.other African American en
dc.subject.other article en
dc.subject.other autophosphorylation en
dc.subject.other controlled study en
dc.subject.other endothelium cell en
dc.subject.other ethnicity en
dc.subject.other European American en
dc.subject.other female en
dc.subject.other gene expression regulation en
dc.subject.other gene frequency en
dc.subject.other gene function en
dc.subject.other gene location en
dc.subject.other gene locus en
dc.subject.other gene structure en
dc.subject.other genetic analysis en
dc.subject.other genetic association en
dc.subject.other genetic risk en
dc.subject.other genetic susceptibility en
dc.subject.other genotype en
dc.subject.other Greece en
dc.subject.other Hispanic en
dc.subject.other human en
dc.subject.other intracellular signaling en
dc.subject.other major clinical study en
dc.subject.other male en
dc.subject.other molecular pathology en
dc.subject.other priority journal en
dc.subject.other risk assessment en
dc.subject.other single nucleotide polymorphism en
dc.subject.other systemic lupus erythematosus en
dc.subject.other vasculotropin receptor 2 gene en
dc.subject.other Adult en
dc.subject.other Case-Control Studies en
dc.subject.other Chi-Square Distribution en
dc.subject.other Endothelial Cells en
dc.subject.other Female en
dc.subject.other Gene Frequency en
dc.subject.other Genetic Predisposition to Disease en
dc.subject.other Greece en
dc.subject.other Humans en
dc.subject.other Lupus Erythematosus, Systemic en
dc.subject.other Male en
dc.subject.other Middle Aged en
dc.subject.other Models, Molecular en
dc.subject.other Odds Ratio en
dc.subject.other Phenotype en
dc.subject.other Phosphorylation en
dc.subject.other Polymorphism, Single Nucleotide en
dc.subject.other Protein Conformation en
dc.subject.other Risk Factors en
dc.subject.other Signal Transduction en
dc.subject.other Structure-Activity Relationship en
dc.subject.other Vascular Endothelial Growth Factor Receptor-2 en
dc.title Implication of VEGFR2 in systemic lupus erythematosus: A combined genetic and structural biological approach en
heal.type journalArticle en
heal.publicationDate 2013 en
heal.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. © Clinical and Experimental Rheumatology 2013. en
heal.journalName Clinical and Experimental Rheumatology en
dc.identifier.issue 1 en
dc.identifier.volume 31 en
dc.identifier.spage 97 en
dc.identifier.epage 102 en


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