title: Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia.
abstract: Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The 'C Glu b' haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the 'C Glu b' haplotype may protect against the development of PE by increasing endogenous NO formation.
authors.affiliation: Nucleo de Pos-Graduacao e Pesquisa da Santa Casa de Belo Horizonte, 30150-221 Belo Horizonte, MG, Brazil.
authors.forename: Valeria C
authors.initials: VC
authors.lastname: Sandrim
authors.forename: Ana C T
authors.initials: AC
authors.lastname: Palei
authors.forename: Jonas T
authors.initials: JT
authors.lastname: Sertorio
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Cavalli
authors.forename: Geraldo
authors.initials: G
authors.lastname: Duarte
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D009569:Nitric Oxide / Q000097:blood*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D009573:Nitrites / Q000097:blood; D011110:Polymorphism, Genetic / Q000235:genetics*; D011225:Pre-Eclampsia / Q000097:blood* / Q000235:genetics*; D011247:Pregnancy; D055815:Young Adult
chemical_list: D009573:Nitrites; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III