Association of VEGF and KDR polymorphisms with the development of schizophrenia

Aim: Several approaches indicate different blood flow disturbances in schizophrenia (Scz). Vascular endothelial growth factor (VEGF) is widely recognized as one of the key molecules implicated in the angiogenesis process through mainly its receptor KDR. The current work was designed to investigate the potential association between three polymorphisms (rs699947; rs833061 and rs3025039) in VEGF gene and two SNPs (rs2305948 and rs1870377) within KDR gene and predisposition to Scz among the Tunisian population. Methods: We carried-out a case-control study composed of 200 schizophrenic patients and 200 healthy subjects using RFLP-PCR. Results: Of all analyzed polymorphisms, only rs3025039, rs833061 and rs1870377 showed a significant risk for Scz. Following the stratified analysis, rs833061 was more prevalent among undifferentiated form. Yet, rs1870377 was especially correlated with paranoid subtype. We found also that rs699947 and rs833061 had an impact on patients9 symptomatology. Haplotype analysis unveiled a strong LD between rs833061 and rs3025039 only for undifferentiated patients. Moreover, the -2578/-460/+936 CTT haplotype, with only one mutated allele +936T, conferred a high risk to Scz and, in particular, to undifferentiated and paranoid forms. Among the last-mentioned subgroup, we noticed another overrepresented haplotype (ATT). Furthermore, the +1192/+1719 GT haplotype carrying the minor allele +1719T displayed increased frequencies in schizophrenics as well as in paranoid patients. Conclusion: Our results show that all SNPs associated with the development or the severity of schizophrenia, were subsequently correlated with a decrease in the VEGF levels or influence VEGFR-2 binding affinity. Nevertheless, these data need to be strengthened by further independent analyses.