title: Kinase insert domain receptor/vascular endothelial growth factor receptor 2 (KDR) genetic variation is associated with ovarian hyperstimulation syndrome.
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.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, DC, USA. phmtjo@gwu.edu.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Arthur F
authors.initials: AF
authors.lastname: Harralson
authors.forename: Tuyen
authors.initials: T
authors.lastname: Tran
authors.forename: Ian
authors.initials: I
authors.lastname: Gindoff
authors.forename: Funda E
authors.initials: FE
authors.lastname: Orkunoglu-Suer
authors.forename: David
authors.initials: D
authors.lastname: Frankfurter
authors.forename: Paul
authors.initials: P
authors.lastname: Gindoff
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000009:adverse effects / Q000494:pharmacology; D004219:District of Columbia; D004351:Drug Resistance; D004958:Estradiol / Q000097:blood; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000009:adverse effects / Q000494:pharmacology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006785:Hospitals, University; D006801:Humans; D015810:Linkage Disequilibrium; D016471:Ovarian Hyperstimulation Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000000981:diagnostic imaging / Q000187:drug effects; D010062:Ovulation Induction / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D014463:Ultrasonography; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006063:Chorionic Gonadotropin; D005300:Fertility Agents, Female; D004958:Estradiol; D005640:Follicle Stimulating Hormone; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2