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

Authors

Travis J. O'Brien, George Washington UniversityFollow
Arthur F. Harralson, George Washington UniversityFollow
Tuyen Tran, Children's National Medical Center
Ian Gindoff, George Washington University
Funda E. Orkunoglu-Suer
David Frankfurter, George Washington University
Paul Gindoff, George Washington University

Document Type

Journal Article

Publication Date

5-9-2014

Journal

Reproductive Biology and Endocrinology

Volume

Volume 12

Inclusive Pages

Article number 36

Keywords

Ovarian Hyperstimulation Syndrome--genetics; Polymorphism, Single Nucleotide; Vascular Endothelial Growth Factor Receptor-2--genetics

Abstract

Background

The 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).

Methods

This 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.

Results

Patients 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).

Conclusions

The 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.

Comments

Reproduced with permission of BioMed Central Reproductive Biology and Endocrinology.

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

O'Brien, T.J., Harralson, A.F., Tran, T., Gindoff, I., Orkunoglu, F.E. et al. (2014). Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome. Reproductive Biology and Endocrinology, 12:36.

Peer Reviewed

1

Open Access

1