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Belo Horizonte, Brazil

Luizon M.R.,University of Sao Paulo | Palei A.C.T.,University of Campinas | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa
Journal of Pregnancy | Year: 2012

Valenzuela and colleagues have recently reviewed some polymorphisms in important candidate genes involved in different pathogenic mechanisms related to preeclampsia (PE) and concluded that various studies in different populations have identified maternal polymorphisms associated with PE. However, we would like to contribute to some studies regarding candidate genes related to angiogenesis and endothelial dysfunction in PE performed in the Brazilian population. Specifically, genotypes and haplotypes formed by polymorphisms of VEGF, eNOS and MMP-9, along with an example of the interaction among these genes in the prediction of PE. Our suggestions may provide additional information with clinical relevance to PE susceptibility. © 2012 Marcelo Rizzatti Luizon et al.

Luizon M.R.,University of Sao Paulo | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa | Palei A.C.T.,University of Campinas | Lacchini R.,University of Sao Paulo | And 3 more authors.
Hypertension Research | Year: 2012

Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and-90(CA) 13-25, rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. © 2012 The Japanese Society of Hypertension All rights reserved.

Sandrim V.C.,Sao Paulo State University | Palei A.C.T.,University of Campinas | Eleuterio N.,Nucleo de Pos Graduacao e Pesquisa | Tanus-Santos J.E.,University of Sao Paulo | Cavalli R.C.,University of Sao Paulo
Archives of Gynecology and Obstetrics | Year: 2015

Introduction: Vascular endothelial growth factor (VEGF) is relevant for healthy pregnancy, and abnormalities in VEGF functions have been associated with hypertensive disorders of pregnancy. Our group recently demonstrated that VEGF genetic polymorphisms affect the susceptibility to preeclampsia (PE). Objective: Therefore, in this study our aim is to examine whether VEGF polymorphisms affect the antihypertensive responses in women with PE. Methods: We studied 113 white PE women who were stratified according to blood pressure levels after antihypertensive treatment (46 responsive, R group and 67 non-responsive, NR group). We then compared the frequencies of two VEGF genetic polymorphisms (C-2578A and G-634C) between R and NR groups. Results: We found no significant differences in genotype or allele distributions between R and NR groups (P > 0.05). In addition, no difference was observed in overall distribution of haplotypes (P > 0.05). Conclusion: Our data suggest that VEGF polymorphisms do not affect responsiveness to the antihypertensive therapy in PE. © 2014, Springer-Verlag Berlin Heidelberg.

Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa | Luizon M.R.,University of Sao Paulo | Izidoro-Toledo T.C.,University of Sao Paulo | Coelho E.B.,University of Sao Paulo | And 2 more authors.
Journal of Human Hypertension | Year: 2013

We examined whether vascular endothelial growth factor (VEGF) polymorphisms (C-2578A, G-1154A and G-634C) are associated with hypertension, response to antihypertensive therapy and nitric oxide (NO) formation. Substudy 1 compared the distribution of VEGF genotypes and haplotypes in 178 patients with arterial hypertension (100 whites and 78 blacks) and 186 healthy controls (115 whites and 71 blacks). Substudy 2 compared the distribution of VEGF markers in 82 patients with controlled hypertension, 89 patients with resistant hypertension and 101 normotensive (NT) patients. In substudy 3, plasma nitrite/nitrate (NOx) levels were determined (chemiluminescence assay) in 64 NT subjects and 48 hypertensive (HTN) subjects, and the distribution of VEGF markers was compared in subjects having low NOx with subjects having high NOx. Although the substudy 1 showed no differences in genotypes or allele distributions for the three VEGF polymorphisms between NT and HTN subjects, the C-A-G haplotype was more common in white NT subjects than in the white HTN subjects, and the C-A-C haplotype was more frequent in black and white HTN subjects than in black and white NT subjects. The substudy 2 showed similar results, with no differences between responsive and resistant HTN subjects. The substudy 3 showed that the C-A-G haplotype, which had a protective effect against hypertension, was significantly more common in subjects with higher NOx concentrations than in subjects with lower NOx concentrations. VEGF haplotypes are associated with hypertension, and the haplotype associated with normotension was more common in subjects with increased NO formation, possibly offering a mechanistic clue for our findings. © 2013 Macmillan Publishers Limited.

Fernandes K.S.D.S.,University of Sao Paulo | Brum D.G.,University of Sao Paulo | Palei A.C.,University of Sao Paulo | Sandrim V.C.,Nucleo de Pos Graduacao e Pesquisa | And 3 more authors.
Journal of Neuroimmunology | Year: 2012

We have described that MMP-9 C -1562T and (CA) n polymorphisms contribute to multiple sclerosis (MS). Here, we evaluate whether plasma MMP-9 levels are related to disease severity, drug therapy resistance and polymorphisms. For sub-study 1, 36 patients with MS and 35 controls were recruited. For sub-study 2, 88 individuals (53 patients and 35 controls) were included in a cross-sectional analysis. MS patients presented higher MMP-9 activity (1.4±0.18 versus 0.93±0.18A.U. for control, P<0.05). Drug-therapy resistant individuals exhibited increased MMP-9 activity (1.96±0.25 versus 1.21±0.09A.U. for non-resistant patients). EDSS score was also related to MMP-9 levels. The CT+TT and HH genotypes had higher MMP-9 levels as compared to patients carrying the CC and LL. Drug therapy resistance, disease severity, MMP-9 plasma activity and polymorphisms are associated with MS. © 2012 Elsevier B.V.

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