title: Maternal iNOS genetic polymorphisms and hypertensive disorders of pregnancy.
abstract: Increased expression and activity of inducible nitric oxide synthase (iNOS) may contribute to the pathogenesis of pre-eclampsia (PE) and gestational hypertension (GH). However, no previous study has examined whether genetic polymorphisms in the iNOS gene are associated with PE or GH. We examined whether two functional, clinically relevant iNOS genetic polymorphisms (the C(-1026)A polymorphism, rs2779249, in the promoter region, and the G2087A polymorphism, rs2297518, in exon 16) are associated with GH or with PE. We studied 565 pregnant women: 212 healthy pregnant (HP), 166 pregnant with GH and 187 pregnant with PE. Genotypes were determined by real-time PCR, using the Taqman allele discrimination assay. The PHASE 2.1 program was used to estimate haplotype distributions in the three study groups. We found no significant association between the C(-1026)A polymorphism and PE or GH (P>0.05). However, we found the GA genotype and the A allele for the G2087A polymorphism at higher frequency in PE, but not in GH, compared with HP (P<0.05). The haplotype analysis showed no significant intergroup differences (P>0.05). These findings suggest that iNOS genetic variants may affect the susceptibility to PE, but not to GH.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Amaral
authors.forename: A C T
authors.initials: AC
authors.lastname: Palei
authors.forename: V C
authors.initials: VC
authors.lastname: Sandrim
authors.forename: M R
authors.initials: MR
authors.lastname: Luizon
authors.forename: R C
authors.initials: RC
authors.lastname: Cavalli
authors.forename: G
authors.initials: G
authors.lastname: Duarte
authors.forename: J E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000328:Adult; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics; D011247:Pregnancy; D055815:Young Adult
chemical_list: C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II