Polymorphisms of VEGF and VEGF receptors are associated with the occurrence of ovarian hyperstimulation syndrome (OHSS)-a retrospective case-control study

Background: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI therapy. The pathophysiology and etiology of the disease is still not fully clarified. Methods: To assess whether polymorphisms of the VEGF/VEGF-receptor system contribute to the occurrence of ovarian hyperstimulation syndrome (OHSS), we performed a retrospective analysis of 116 OHSS patients, and 124 female controls. The following SNPs were genotyped: Rs2071559 (VEGFR2- 604); rs2305948 (VEGFR2- 1192); rs1870377 (VEGFR2- 1719); rs2010963 (VEGF-405); and rs111458691 (VEGFR1-519). Odds ratios (ORs) were estimated with a 95% confidence interval (CI). Linkage disequilibrium (LD) analysis was performed in the three loci of the VEGFR2 gene. Result: We found an overrepresentation of the T allele of the VEGFR1-519 polymorphism in OHSS patients (P = 0.02, OR: 3.62, CI: 1.16-11.27). By genotype modeling, we found that polymorphism of VEGFR1-519 and VEGF- 405 showed significant differences in patients and controls (p = 0.02, OR: 3.79 CI: 1.98-11.97 and p = 0.000005, OR: 0.29, CI: 0.17-0.50). LD analysis revealed significant linkage disequilibrium in VEGFR2. Conclusion: Polymorphisms in the VEGFR2 gene and in the VEGF gene are associated with the occurrence of OHSS. This strengthens the evidence for an important role of the VEGF/VEGF-receptor system in the occurrence of OHSS.