title: Synergistic effects of angiotensinogen -217 G→A and T704C (M235T) variants on the risk of severe preeclampsia.
abstract: BACKGROUND
  The rate-limiting step of the renin-angiotensin system is the enzymatic cleavage of angiotensinogen (AGT) by renin. The aims of the present study were to investigate the association between AGT T704C (M235T) and -217 G→A polymorphisms with the risk of preeclampsia and synergistic effects of both polymorphisms on the susceptibility to preeclampsia.
  
  
  METHODS
  We studied AGT variants in 170 women with preeclampsia, including 84 women with mild and 86 women with severe forms of preeclampsia, and 100 age and parity matched controls.
  
  
  RESULTS
  There was a trend towards increased risk of severe preeclampsia in the presence of -217 AA (odds ratio (OR)=1.5, 95% confidence interval (CI)= 0.38-5.84, p=0.57) and TC+CC genotypes (OR=1.32, 95% CI= 0.67-2.58, p=0.42). However, the interaction of both alleles of -217A and 704C highly increased the risk of severe preeclampsia, by 2.23-fold, although this did not reach statistical significance. The frequency of the CC genotype of the T704C polymorphism in early-onset preeclampsia tended to be higher (35%) compared with that in patients with late-onset preeclampsia (21.7%).
  
  
  CONCLUSIONS
  The present study demonstrates that both variants of AGT -217 G→A and T704C might work in synergism to influence the risk of severe preeclampsia, which needs to be confirmed in studies with larger sample size.
authors.affiliation: Department of Medical Genetics, Medical School, Shahid Beheshti University of Medical Sciences, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Shahvaisizadeh
authors.affiliation: Department of Medical Genetics, Medical School, Shahid Beheshti University of Medical Sciences, Iran.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Movafagh
authors.affiliation: Department of Medical Genetics, Medical School, Shahid Beheshti University of Medical Sciences, Iran.
authors.forename: Mir Davood
authors.initials: MD
authors.lastname: Omrani
authors.affiliation: Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Iran.
authors.forename: Asad
authors.initials: A
authors.lastname: Vaisi-Raygani
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Iran.
authors.forename: Ziba
authors.initials: Z
authors.lastname: Rahimi
authors.affiliation: Department of Biochemistry, Medical School, Kermanshah University of Medical Sciences, Iran Medical Biology Research Center, Kermanshah University of Medical Sciences, Iran zrahimi@kums.ac.ir.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Rahimi
mesh_terms: D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012306:Risk
chemical_list: D000808:Angiotensinogen