AUTHOR=Pereira Daniela A. , Luizon Marcelo R. , Palei Ana C. , Tanus-Santos José E. , Cavalli Ricardo C. , Sandrim Valeria C. 

TITLE=Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1293082

DOI=10.3389/fgene.2024.1293082

ISSN=1664-8021

ABSTRACT=<p>Impaired nitric oxide (NO) formation may be associated with endothelial dysfunction and increased cardiovascular disease risk in preeclampsia (PE). Functional single-nucleotide polymorphisms (SNPs) of nitric oxide synthase 3 (<italic>NOS3</italic>) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (<italic>GUCY1A3</italic>) (rs7692387) increase susceptibility to the adverse consequences due to inadequate generation of NO by the endothelium. However, no previous study has examined whether these SNPs affect NO formation in healthy pregnancy and in gestational hypertension (GH) and PE. Here, we compared the alleles and genotypes of <italic>NOS3</italic> (rs3918226) and <italic>GUCY1A3</italic> (rs7692387) SNPs in normotensive pregnant women (NP, <italic>n</italic> = 153), in GH (<italic>n</italic> = 96) and PE (<italic>n</italic> = 163), and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. We further examined whether the interaction among SNP genotypes is associated with GH and PE. Genotypes were determined using TaqMan allele discrimination assays, and plasma nitrite concentrations were determined by an ozone-based chemiluminescence assay. Multifactor dimensionality reduction was used to examine the interactions among SNP genotypes. Regarding <italic>NOS3</italic> rs3918226, the CT genotype (<italic>p</italic> = 0.046) and T allele (<italic>p</italic> = 0.020) were more frequent in NP than in GH, and GH patients carrying the CT+TT genotypes showed lower nitrite concentrations than NP carrying the CT+TT genotypes (<italic>p</italic> &lt; 0.05). Regarding <italic>GUCY1A3</italic> rs7692387, the GA genotype (<italic>p</italic> = 0.013) and A allele (<italic>p</italic> = 0.016) were more frequent in PE than in NP, and NP women carrying the GG genotype showed higher nitrite concentrations than GH or PE patients carrying the GG genotype (<italic>p</italic> &lt; 0.05). However, we found no significant interactions among genotypes for these functional SNPs to be associated with GH or PE. Our novel findings suggest that <italic>NOS3</italic> rs3918226 and <italic>GUCY1A3</italic> rs7692387 may affect NO formation and association with hypertensive disorders of pregnancy.</p>