eNOS Tag SNP Haplotypes in Hypertensive Disorders of Pregnancy

Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The aim of the current study was to compare the distribution of the genotypes and haplotypes formed by the five eNOS polymorphisms mentioned among healthy pregnant (HP, n = 122), GH (n = 138), and PE (n = 157). The haplotype formed by "C b G G C" was more frequent in HP compared to GH and PE (p = 0.0071), which is supported by previous findings that demonstrated the association of the combination "C b G" with a higher level of nitrite (NO marker). Our results suggest a protective effect of the haplotype "C b G G C" against the development of hypertensive disorders of pregnancy.

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.-1562C>T and g.-90(CA)(13-25)) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.-90(CA)(13-25) polymorphism were grouped L (low) (<21 CA repeats) or H (high) (>= 21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.-90(CA)(13-25) polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.-1562C>T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy. The Pharmacogenomics Journal (2012) 12, 489-498; doi: 10.1038/tpj.2011.31; published online 19 July 2011

Vitamin D receptor polymorphisms in hypertensive disorders of pregnancy

Hypertension is the most common medical disorder in pregnancy, and a leading cause of maternal and neonatal morbidity and mortality. Vitamin D endocrine system has important influence on immune modulation and endothelial function, which play a role in preeclampsia (PE) and gestational hypertension (GH). Vitamin D receptor (VDR) is present in a large variety of cell types, including placental cells. We examined whether there is an association between VDR polymorphisms (FokI, ApaI and BsmI) with PE or with GH. Restriction fragment length polymorphism techniques were used to genotype 529 pregnant (154 with GH, 162 with PE, and 213 healthy pregnant-HP). VDR haplotype frequencies were inferred using the PHASE 2.1 program. We found similar genotype distributions for the three VDR polymorphisms in both PE and GH groups compared with the HP group (all P > 0.05). In parallel with these findings, the VDR haplotype frequency distribution was similar in both PE and GH groups compared with the HP group (all P > 0.05). Our results showing no significant association between VDR polymorphisms or haplotypes with PE or GH suggest that genetic variations in VDR do not predispose to hypertensive disorders of pregnancy.

Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy

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 (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). 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 (P<0.05). 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. Hypertension Research (2012) 35, 917-921; doi:10.1038/hr.2012.60; published online 10 May 2012

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306 C> T and g.-735 C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306 C>T and g.-735 C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306 C>T and g.-735 C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined. (C) 2012 Elsevier Inc. All rights reserved.

Effects of Matrix Metalloproteinase (MMP)-2 Polymorphisms on Responsiveness to Antihypertensive Therapy of Women with Hypertensive Disorders of Pregnancy

Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.-1306C>T and g.-735C>T) are associated with pre-eclampsia and/or gestational hypertension and whether these polymorphisms affect therapeutic responses in women with these conditions. We studied 216 healthy pregnant women (HP), 185 patients with gestational hypertension (GH) and 216 patients with pre-eclampsia (PE). They were stratified as responsive or non-responsive to antihypertensive therapy according to clinical and laboratorial parameters of therapeutic responsiveness. Genomic DNA was extracted from whole blood and genotypes for g-1306C>T and g.-735C>T polymorphisms were determined by real-time PCR using Taqman allele discrimination assays. Haplotype frequencies were inferred using the PHASE 2.1 program. The distributions of MMP-2 genotypes and haplotypes were similar in HP, GH and PE patients (p > 0.05). In addition, we found no significant differences in MMP-2 genotype or haplotype frequencies when GH or PE patients were classified as responsive or non-responsive to antihypertensive therapy (p > 0.05). Our results suggest that MMP-2 polymorphisms do not affect the susceptibility to hypertensive disorders of pregnancy. In parallel, MMP-2 polymorphisms apparently do not affect the responsiveness to antihypertensive therapy of women with these hypertensive disorders of pregnancy.

Genetic diversity of the Brazilian Creole cattle Pe-duro assessed by microsatellites and mitochondrial DNA

The objective of this study was to describe the genetic diversity and structure of the largest Pe-duro population by assessing variation at ten autosomal microsatellite (STR) loci and mitochondrial DNA (mtDNA) sequences. The mean expected heterozygosity was 0.755, the mean observed heterozygosity was 0.600 and significant inbreeding coefficient (Fis) and deviations from the Hardy-Weinberg equilibrium in most of analyzed loci demonstrate the impact of inbreeding and homozygosis on this population. A more in-depth genetic analysis could be achieved by expanding the STR list. The analysis of mtDNA provided evidence of ancestral African taurine haplotypes in Pe-duro and excluded maternal Zebuine introgression. In this report, the main Pe-duro population is genetically portrayed by sampling approximately 40% of it. As this herd represents the core of the Pe-duro conservation program, these findings are of outstanding value for the management and preservation of this Brazilian 'native' cattle breed.

Lipid fingerprinting in women with early-onset preeclampsia: A first look

Objectives: The aim of this preliminary study was to characterize the plasma lipid profiling of women with preeclampsia. Design and methods: Plasma samples of 8 pregnant women with early-onset preeclampsia and 8 normal pregnant women were evaluated. Lipids were extracted from plasma using the Bligh-Dyer protocol. The extracts were subjected to MALDI-MS. Data matrix was exported for partial least squares discriminant analysis (PLS-DA) and a parameter VIP was employed to reflect the variable importance in the discriminant analysis. The major discriminant variables were selected and underwent to Mann-Whitney U test. Results: A total of 1290 ions were initially identified and twelve m/z signals were highlighted as the most important lipids for the discrimination of patients with preeclampsia. The identification of these differential lipids was carried out through Lipid Database Search. Conclusions: The main classes identified were glycerophosphocholines [GP01], glycerophosphoserines [GP03], glycerophosphoglycerols [GP04], glycosyldiradylglycerols [GL05] and glycerophosphates [GP10]. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Maternal iNOS genetic polymorphisms and hypertensive disorders of pregnancy

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. Journal of Human Hypertension (2012) 26, 547-552; doi:10.1038/jhh.2011.65; published online 30 June 2011

Avaliação do processo de sedimentação recente na Bacia do Pina – Recife (PE) Brasil – por meio do uso da variação vertical de carbonato biodetrítico e susceptibilidade magnética

O sistema estuarino-lagunar da Bacia do Pina e Rio Capibaribe situa-se no Recife (PE) Brasil, formado pela confluência dos rios Capibaribe, Tejipió, Jiquiá, Jordão e Pina, de grande importância para a Região Metropolitana do Recife. A variação vertical da porcentagem de carbonato de cálcio (CaCO3) no ambiente e a susceptibilidade magnética são ferramentas utilizadas para identificar o processo sedimentar dominante durante a deposição em ambientes costeiros e marinhos, podendo ser de origem marinha ou continental. Foi recuperado um testemunho, com 109 cm, localizado no setor médio do sistema estuarino. Os valores de susceptibilidade foram obtidos com o medidor da marca Bartington MS 2C, descritos visualmente quanto a granulometria e estruturas sedimentares, sub-amostrados em intervalos de 2 cm para a %CaCO3. Os valores de susceptibilidade variaram de 1 a 24 SI, os valores de carbonato variaram de 1,56 a 41,17 %. De acordo com a descrição visual foi observado a presença de granocrescência ascendente entre areia fina a média, cascalho biodetríticos, fragmentos de CaCO3, camadas de lama com matéria orgânica, fragmentos plásticos em algumas profundidades e a presença de uma camada de cascalho terrígeno. Por ser um ambiente de transição continental/marinho, a variação da sedimentação possivelmente está associada ao regime pluviométrico, onde em períodos chuvosos o sedimento fino presente no ambiente é remobilizado, e no período seco a pouca vazão fluvial favorece a deposição de finos. No intervalo 14 – 16 cm foi observado a maior porcentagem de CaCO3 indicando influência marinha durante a sedimentação. Diversos pulsos de sedimentação predominantemente terrígena foram observados na coluna sedimentar, representados por picos mais altos de susceptibilidade magnética provavelmente associados à ciclicidade das cheias do rio Capibaribe. As variações verticais de carbonato e da susceptibilidade obtidas foram importantes na identificação da variabilidade de influência terrígena ou marinha durante o processo de sedimentação recente no estuário