title: Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis.
abstract: BACKGROUND
  Angiogenesis and an adequate blood supply are critical for several steps in human early pregnancy. Some studies have reported angiogenesis- and vasoconstriction-related genes are associated with recurrent pregnancy loss (RPL), but their sample size was limited. This study was conducted to investigate the genetic association between these angiogenesis- and vasoconstriction-related genes and idiopathic RPL, using meta-analyses.
  
  
  METHODS
  A systematic review of the published literature from MEDLINE and EMBASE databases was conducted and investigations of an angiogenesis- and vasoconstriction-related gene polymorphism in RPL reported more than three times were selected. Aggregating data from eligible studies were integrated into meta-analyses by means of random effects models.
  
  
  RESULTS
  Of 185 potentially relevant studies, 18 case-control studies comprising a total of 2397 RPL patients and 1760 controls were included into the meta-analyses. Among these genetic association studies were 4 reports of vascular endothelial growth factor (VEGF) (-1154G>A) polymorphisms, 4 reports of p53 (codon72) and 10 reports of endothelial nitric oxide synthase (eNOS) (B/A, Glu298Asp) with RPL. The integrated results showed that VEGF (-1154G>A), p53 (codon 72) and eNOS (Glu298Asp) polymorphisms were significantly associated with RPL, and their summary odd ratios [95% confidence interval (CI)] were 1.51 (1.13-2.03), 1.84(1.07-3.16) and 1.37 (1.11-1.69), respectively. The summary odd ratio of the eNOS (B/A) polymorphism in RPL was 1.15 (0.94-1.41), and failed to show significance at meta-analysis.
  
  
  CONCLUSIONS
  Meta-analyses of available data showed significant associations between the VEGF (-1154G>A), p53 (codon72) and eNOS (Glu298Asp) polymorphisms and idiopathic RPL. These angiogenesis- and vasoconstriction-related genes jointly confer higher susceptibility to idiopathic RPL.
authors.affiliation: Division of Genetics, Department of Obstetrics and Gynecology, National Cheng Kung University College of Medicine, 138 Sheng-Li Road, Tainan 704, Taiwan. sumeitsz@mail.ncku.edu.tw
authors.forename: Mei-Tsz
authors.initials: MT
authors.lastname: Su
authors.forename: Sheng-Hsiang
authors.initials: SH
authors.lastname: Lin
authors.forename: Yi-Chi
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D016158:Genes, p53; D056726:Genetic Association Studies; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D014661:Vasoconstriction / Q000235:genetics*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III