Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome

Abstract

BackgroundThe objective of this investigation was to determine if kinase insert domain/vascular endothelial growth factor receptor 2 (KDR/VEGFR2) genetic variation was associated with the development of ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation (COH).MethodsThis was a case–control study of 174 patients who underwent controlled ovarian stimulation. Patient blood samples were genotyped for single nucleotide polymorphisms (SNPs) spanning the KDR locus. OHSS development, clinical outcome variables, SNP and haplotype frequencies were compared between control (n = 155) and OHSS (n = 19) groups.ResultsPatients who developed OHSS had significantly higher response markers (estradiol levels of the day of hCG administration, number of follicles developed, number of eggs retrieved) than control patients. When adjusted for age and self-identified race, the rs2305945 G/T genotype was associated (P = 0.027) with a decreased risk (OR = 0.30; 95% CI = 0.10, 0.93) of developing OHSS using an overdominant model. The rs2305945 G/T variant was also associated with decreased COH response (number of follicles, number of eggs retrieved) in an overdominant model. The rs2305948, rs1870378, rs2305945 (C-T-G) haplotype was associated with both decreased COH response and OHSS risk (unadjusted OR = 0.10; 95% CI = 0.01, 0.80, P = 0.031).ConclusionsThe KDR receptor is believed to play a central role OHSS development and is a target for pharmacological prevention of OHSS. These results indicate that genetic variation in the KDR gene may impact individual risk of developing OHSS from COH. In addition, the rs2305948 SNP and C-T-G haplotype might serve as potential biomarkers for poor ovarian response to COH.

Genetic Variations of Kinase Inserts Domain Receptor (KDR) Gene Are Associated with the Risk of Astrocytomas

“…For example, Jang et al found KDR SNPs (1192G>A) could reduce the risk of colorectal cancer in Koreans [33]. KDR variation (rs2305945, G/T) can lead to ovarian hyperstimulation syndrome in Travis's research [34]. Zheng et al discovered KDR polymorphisms with vascular malformation [35].…”

c-MET/VEGFR-2 co-localisation impacts on survival following bevacizumab therapy in epithelial ovarian cancer: an exploratory biomarker study of the phase 3 ICON7 trial

“…Although this SNP is located within a non-coding region of VEGFR-2 , there are data suggesting it is of clinical interest. Indeed, previous data has reported that rs2305945 is associated with differential response to VEGF inhibitors in age-related macular degeneration and also protective against ovarian hyperstimulation syndrome [ 29 , 30 ]. The latter is of particular relevance here given the physiological importance of VEGF to follicular cysts formation and the plethora of trials that have demonstrated the clinical activity of VEGF inhibitors in ovarian cancer, irrespective of the platinum/progression-free interval.…”