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

Reproductive Biology and Endocrinology

Paul Gindoff⁵  David Frankfurter⁵  Funda E Orkunoglu-Suer²  Ian Gindoff³  Tuyen Tran¹  Arthur F Harralson⁴  Travis J O’Brien³ 

[1] Center for Neuroscience, Children’s National Medical Center, Washington, DC 20010, USA;Quest Diagnostics, Athena Diagnostics, Worcester, MA 01605, USA;Department of Pharmacology and Physiology, The George Washington University, Washington, DC, USA;Department of Pharmacogenomics, Bernard J. Dunn School of Pharmacy, Shenandoah University, Ashburn, VA, USA;Department of Obstetrics and Gynecology, The George Washington University, Washington, DC, USA

关键词: Polymorphism;    VEGFR2;    KDR;    OHSS;    Ovarian hyperstimulation syndrome;    Ovarian stimulation;   

Others  :  804274
DOI  :  10.1186/1477-7827-12-36

 received in 2014-03-20, accepted in 2014-05-01,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 O’Brien et al.; licensee BioMed Central Ltd.

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