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.


RESULTS
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.


CONCLUSIONS
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.
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Kazem
K
Nouri
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Peter
P
Haslinger
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Ladislaus
L
Szabo
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria ; Privatklinik Doebling, Fertility Center Doebling, Vienna, Austria.
Michael
M
Sator
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Martin
M
Schreiber
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Christian
C
Schneeberger
Department of Endocrinology and Reproductive Medicine, Medical University Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Detlef
D
Pietrowski
D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D016471:Ovarian Hyperstimulation Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
ART; IVF-therapy; OHSS; VEGF; Vascular permeability