Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy
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 (NOS3) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) (rs7...
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| Formato: | Artigo |
| Idioma: | English |
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Frontiers Media S.A.
2024-02-01
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| coleção: | Frontiers in Genetics |
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| Acesso em linha: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1293082/full |
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| author | Daniela A. Pereira Marcelo R. Luizon Marcelo R. Luizon Ana C. Palei José E. Tanus-Santos Ricardo C. Cavalli Valeria C. Sandrim |
| author_facet | Daniela A. Pereira Marcelo R. Luizon Marcelo R. Luizon Ana C. Palei José E. Tanus-Santos Ricardo C. Cavalli Valeria C. Sandrim |
| author_sort | Daniela A. Pereira |
| collection | DOAJ |
| description | 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 (NOS3) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) (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 NOS3 (rs3918226) and GUCY1A3 (rs7692387) SNPs in normotensive pregnant women (NP, n = 153), in GH (n = 96) and PE (n = 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 NOS3 rs3918226, the CT genotype (p = 0.046) and T allele (p = 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 (p < 0.05). Regarding GUCY1A3 rs7692387, the GA genotype (p = 0.013) and A allele (p = 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 (p < 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 NOS3 rs3918226 and GUCY1A3 rs7692387 may affect NO formation and association with hypertensive disorders of pregnancy. |
| first_indexed | 2024-03-07T21:43:06Z |
| format | Article |
| id | doaj.art-06263f444b1e4f199a38e70ba15c81c2 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-07T21:43:06Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-06263f444b1e4f199a38e70ba15c81c22024-02-26T04:29:56ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-02-011510.3389/fgene.2024.12930821293082Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancyDaniela A. Pereira0Marcelo R. Luizon1Marcelo R. Luizon2Ana C. Palei3José E. Tanus-Santos4Ricardo C. Cavalli5Valeria C. Sandrim6Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartment of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, BrazilDepartment of Surgery, University of Mississippi Medical Center, Jackson, MS, United StatesDepartment of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, BrazilDepartment of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirão Preto, BrazilDepartment of Biophysics and Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, BrazilImpaired 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 (NOS3) (rs3918226) and guanylate cyclase 1, soluble, alpha 3 (GUCY1A3) (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 NOS3 (rs3918226) and GUCY1A3 (rs7692387) SNPs in normotensive pregnant women (NP, n = 153), in GH (n = 96) and PE (n = 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 NOS3 rs3918226, the CT genotype (p = 0.046) and T allele (p = 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 (p < 0.05). Regarding GUCY1A3 rs7692387, the GA genotype (p = 0.013) and A allele (p = 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 (p < 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 NOS3 rs3918226 and GUCY1A3 rs7692387 may affect NO formation and association with hypertensive disorders of pregnancy.https://www.frontiersin.org/articles/10.3389/fgene.2024.1293082/fullgenetic polymorphismsgestational hypertensionguanylate cyclase 1 soluble alpha 3nitric oxidenitric oxide synthase 3preeclampsia |
| spellingShingle | Daniela A. Pereira Marcelo R. Luizon Marcelo R. Luizon Ana C. Palei José E. Tanus-Santos Ricardo C. Cavalli Valeria C. Sandrim Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy Frontiers in Genetics genetic polymorphisms gestational hypertension guanylate cyclase 1 soluble alpha 3 nitric oxide nitric oxide synthase 3 preeclampsia |
| title | Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy |
| title_full | Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy |
| title_fullStr | Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy |
| title_full_unstemmed | Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy |
| title_short | Functional polymorphisms of NOS3 and GUCY1A3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy |
| title_sort | functional polymorphisms of nos3 and gucy1a3 affect both nitric oxide formation and association with hypertensive disorders of pregnancy |
| topic | genetic polymorphisms gestational hypertension guanylate cyclase 1 soluble alpha 3 nitric oxide nitric oxide synthase 3 preeclampsia |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1293082/full |
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