title: Gene-gene interactions and risk of recurrent miscarriages in carriers of endocrine gland-derived vascular endothelial growth factor and prokineticin receptor polymorphisms.
abstract: OBJECTIVE
  To study endocrine gland-derived vascular endothelial growth factor (EG-VEGF), prokineticin receptor (PROKR) 1, and PROKR2 variants in the coding regions of idiopathic recurrent miscarriage (RM) patients and further evaluate gene-gene interactions of these three genes.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  University-based reproductive clinics and genetics laboratory.
  
  
  METHODS
  A total of 142 women with a history of idiopathic RM and 149 control subjects were included.
  
  
  METHODS
  None.
  
  
  METHODS
  All blood samples were nucleotide sequenced in the coding regions of EG-VEGF, PROKR1, and PROKR2. Gene-gene interaction of three gene variants was evaluated with the use of the multifactor dimensionality reduction method.
  
  
  RESULTS
  One nonsynonymous variant of each of the three genes was identified, and PROKR1 (I379V) and PROKR2 (V331M) were significantly associated with idiopathic RM. Genetic interactions were found not only between PROKR1 (I379V) and PROKR2 (V331M), but also among EG-VEGF (V67I), PROKR1 (I379V), and PROKR2 (V331M). Women carrying low-risk genotypes had a 77% reduced risk of experiencing miscarriages compared with those carrying high-risk genotypes.
  
  
  CONCLUSIONS
  The present study corroborates the clinical relevance of the EG-VEGF system in human early pregnancy, and provides evidence for the gene-gene interactions of EG-VEGF and PROKR variants.
authors: Departments of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Mei-Tsz
authors: MT
authors: Su
authors: Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Sheng-Hsiang
authors: SH
authors: Lin
authors: Department of Economics, National Cheng Kung University, Tainan, Taiwan.
authors: Yi-Chi
authors: YC
authors: Chen
authors: Departments of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. Electronic address: paolink@mail.ncku.edu.tw.
authors: Pao-Lin
authors: PL
authors: Kuo
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005768:Gastrointestinal Hormones / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D012307:Risk Factors; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000235:genetics*
chemical_list: D005768:Gastrointestinal Hormones; C467610:PROK1 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
keywords: EG-VEGF; Gene-gene interaction; gene polymorphism; prokineticin receptor; recurrent miscarriage