Open AccessSynergistic effect of renin‐angiotensin system and nitric oxide synthase genes polymorphisms in pre‐eclampsia
Author(s) -
BENEDETTO CHIARA,
MAROZIO LUCA,
CICCONE GIOVANNINO,
CHIEPPA GIUSEPPINA,
QUAGLIA MARCO,
MATULLO GIUSEPPE,
BERTOLA LAURA,
GUARRERA SIMONETTA,
CARTURAN SONIA,
STRATTA PIERO
Publication year - 2007
Publication title -
acta obstetricia et gynecologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.401
H-Index - 102
eISSN - 1600-0412
pISSN - 0001-6349
DOI - 10.1080/00016340701415269
Subject(s) - medicine , endocrinology , renin–angiotensin system , angiotensin ii , preeclampsia , angiotensin converting enzyme , nitric oxide , nitric oxide synthase , eclampsia , biology , pregnancy , receptor , genetics , blood pressure
Background . Components of the renin‐angiotensin system and endothelial nitric oxide synthase may co‐operate in spiral artery remodelling during placentation, and thus reduce the uteroplacental resistance typical of normal pregnancy. Since lack of such remodelling and abnormal placentation are specific features of pre‐eclampsia, it has been suggested that abnormal function of both components of the renin‐angiotensin system and endothelial nitric oxide synthase may be involved in its pathogenesis. However, previous studies of the association between pre‐eclampsia and polymorphisms of single genes encoding renin‐angiotensin system components and endothelial nitric oxide synthase have yielded conflicting results. The aim of this study was to assess if interactions among different polymorphisms of the renin‐angiotensin system and nitric oxide synthase are involved in the pathogenesis of pre‐eclampsia. Methods . Some 359 pregnant women were enrolled: 103 normotensive, 50 with chronic hypertension, 86 with gestational hypertension, and 120 with pre‐eclampsia. DNA analysis was performed to evaluate angiotensin‐converting enzyme I/D, angiotensin‐II receptor 1 1166A/C, angiotensinogen M235T and endothelial constitutive nitric oxide synthase 4b/a polymorphisms. Odds ratios (OR) with 95% confidence interval (CI) and χ 2 tests were calculated. Results . The frequency of single gene polymorphisms was similar in each group. The frequency of pairs including the DD genotype of the angiotensin‐converting enzyme I/D polymorphism plus other homozygous genotypes was significantly higher in pre‐eclamptic patients than in controls (OR = 3.04, 95% CI = 1.16–7.93). Conclusions . Synergism of angiotensin‐converting enzyme I/D and other polymorphisms of renin‐angiotensin system components and nitric oxide synthase may be a risk factor for pre‐eclampsia.