title: eNOSI4 and EPHX1 polymorphisms affect maternal susceptibility to preeclampsia: analysis of five polymorphisms predisposing to cardiovascular disease in 279 Caucasian and 241 African women.
abstract: OBJECTIVE
  The aim of this study was to evaluate possible associations of genetic polymorphisms predisposing to cardiovascular disease with the development and/or the severity of preeclampsia.
  
  
  METHODS
  A two hospital-based prospective case-control study was performed in Germany and Ghana. 470 blood samples of 250 Caucasian and 220 black African have been genotyped by pyrosequencing and fragment length analysis. We evaluated the distribution of the epoxide hydrolase 1 (EPHX1) polymorphism on exon 3, the endothelial nitric oxide synthase (eNOS) polymorphisms on exon 7 and on intron 4, the angiotensinogen polymorphism on exon 2 and the estrogen receptor 1 polymorphism in intron 1.
  
  
  RESULTS
  74 Caucasian and 84 African were classified as preeclampsia with 27 Caucasian developing a hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and 17 African women experiencing eclampsia. Multivariate logistic regression analysis adjusting for ethnicity, age and parity revealed for carriers of eNOSI4 VNTR4a a 1.7-fold increased (95% CI 1.10-2.711, p = 0.016) risk to develop preeclampsia and a 3.6-fold increase for carriers of the EPHX1 113Tyr (95% CI 1.366-8.750, p = 0.009) to develop severest preeclampsia.
  
  
  CONCLUSIONS
  Our finding of eNOSI4 polymorphism predisposing to preeclampsia independently of ethnicity, age and parity supports the concept of NO being involved in the endothelial disorder preeclampsia. Since EPHX1 is highly expressed in the liver, can interact with various signaling pathways and is involved in central nervous system disorders, the association of EPHX1 polymorphism with the HELLP syndrome and eclampsia may hint to EPHX being a further key player in the pathogenesis of preeclampsia.
authors.affiliation: Department of Obstetrics, University Hospital Jena, Bachstrasse 18, 07743, Jena, Germany, tanja.groten@med.uni-jena.de.
authors.forename: T
authors.initials: T
authors.lastname: Groten
authors.forename: E
authors.initials: E
authors.lastname: Schleussner
authors.forename: T
authors.initials: T
authors.lastname: Lehmann
authors.forename: F
authors.initials: F
authors.lastname: Reister
authors.forename: B
authors.initials: B
authors.lastname: Holzer
authors.forename: K A
authors.initials: KA
authors.lastname: Danso
authors.forename: R
authors.initials: R
authors.lastname: Zeillinger
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005091:Exons; D005260:Female; D005838:Genotype; D005858:Germany; D005869:Ghana; D006801:Humans; D007438:Introns; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011446:Prospective Studies; D044465:White People / Q000235:genetics*
chemical_list: D047628:Estrogen Receptor alpha; D000808:Angiotensinogen; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human