Periodontopathogens levels and clinical response to periodontal therapy in individuals with the interleukin-4 haplotype associated with susceptibility to chronic periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Polymorphisms in endothelial nitric oxide synthase gene in early and late severe preeclampsia

Preeclampsia (PE) is characterized by hypertension and proteinuria, occurring after the 20th week of pregnancy in women who have had no previous symptoms. The disease progresses with generalized vasoconstriction and endothelial dysfunction. Clinically, it is important to diagnose the severe form of the disease (sPE), in which blood pressure and proteinuria are much higher. Recently, the gestational age (GA) of the onset of PE has led to the classification of this disease as early (GA <34 weeks) and late (GA >= 34 weeks). Several genetic polymorphisms affecting endothelial nitric oxide synthase (eNOS) levels or function were described, including G894T (Glu298Asp), VNTR b/a (variable-number 27-bp tandem repeat) and T-786C (promoter) polymorphisms. Thus, the aim of this study was to compare the distribution of G894T, VNTR b/a and T-786C polymorphisms and their haplotypes in Brazilian early and late sPE, as well as in normotensive pregnant. A total of 201 women were evaluated, 53 with early sPE, 45 with late sPE and 103 as normotensive pregnant women. The frequency of 894T allele was higher in late sPE vs normotensive pregnant, and 894TT genotype was higher in late sPE vs early sPE and normotensive pregnant. For VNTR b/a polymorphism, higher frequencies of aa genotype and a allele were observed in early sPE vs late sPE and normotensive pregnant. Besides, the frequency of haplotype T-b-C was higher in late sPE vs early sPE and normotensive pregnant. Considering the results found for eNOS polymorphisms, it is possible to suggest that the functional alterations induced by these two polymorphisms may influence the time of severe PE onset, although both alterations are putatively associated with low NO bioavailability. However, other studies are necessary to validate these findings and clarify this issue. (C) 2014 Elsevier Inc. All rights reserved.

Clinical outcomes of periodontal therapy are not influenced by the ATC/TTC haplotype in the IL8 gene

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Linkage disequilibrium and haplotype block structure in a composite beef cattle breed

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência dos polimorfismos para o gene da sintase do óxido nitrico endotelial (eNOS) na pressão arterial e perfil lipídico em resposta ao treinamento físico em mulheres no climatério

A incidência de doenças cardiovasculares tem se constituído na maior causa de morbimortalidade em todo mundo, especialmente após os 50 anos de idade, e têm sido associadas à presença de polimorfismos em alguns genes, especialmente o gene da eNOS. Apesar das mulheres compartilharem com os homens os diversos fatores de risco para o desenvolvimento das doenças cardiovasculares, entre elas hipertensão arterial e dislipidemia, estudos epidemiológicos mostram que as mesmas, antes da menopausa, apresentam menor risco cardiovascular quando comparadas aos homens. Entretanto, após o período da menopausa há um aumento significativo na incidência de hipertensão arterial e suas complicações. Este fato parece estar relacionado a uma possível ação protetora exercida pelos hormônios sexuais femininos, sobretudo os estrogênios que apresentam queda abrupta no período da menopausa. O óxido nítrico (NO), produzido pelas células endoteliais através da enzima eNOS, desempenha importante papel no sistema cardiovascular, participando na regulação do fluxo sanguíneo, do remodelamento vascular e na atividade plaquetária. Assim, estudos envolvendo o gene responsável pela síntese da enzima eNOS, tem sido foco de várias pesquisas na tentativa de avaliar se a presença dos polimorfismos poderia predispor os indivíduos a maior incidência de doenças cardiovasculares. O polimorfismo do gene da eNOS na posição G894T/Glu298Asp localizado no éxon 7, implica na alteração da sequência protéica, tornando a proteína mais suscetível à clivagem, tendo consequências funcionais como a redução do NO demonstrando assim sua provável contribuição para a disfunção endotelial e consequente aumento da pressão arterial. Com relação ao Íntron 4 caracterizado por um Número Variável de Repetições em Tandem... (Resumo completo, clicar acesso eletrônico abaixo)

Polimorfismos do gene da eNOS: relação com hipertensão arterial em diferentes níveis de atividade física em adultos

A gênese da hipertensão arterial têm sido associada à presença de polimorfismos em alguns genes, em específico no gene da eNOS. O polimorfismo no Íntron 4 é caracterizado por um Número Variável de Repetições em Tandem, no qual o alelo 4a foi relacionado a baixos níveis de nitrito/nitrato. Os indivíduos 4a/a exibiram 20% menos óxido nítrico (NO) que os indivíduos com genótipos 4b/b, assim como diminuições na expressão protéica da eNOS. Acredita-se que a alteração polimórfica de único nucleotídeo (SNP), na posição - 786 do gene da eNOS esteja relacionada à modulação do gene através da ação de uma proteína repressora chamada de RPA1, capaz de diminuir a quantidade de mRNA, e nitrito/nitrato plasmático; demonstrando sua provável contribuição para o aumento dos valores de pressão arterial. Apenas dois trabalhos mostram uma associação entre os polimorfismos do Intron 4 e -786, demonstrando que o 4a/4a apresenta uma possível ligação de desequilíbrio com a posição -786, sugerindo uma associação positiva entre polimorfismos e prevalência de espasmos coronários e redução na produção endotelial de NO. No entanto, nenhum trabalho avaliou a associação entre o nível de atividade física e a presença de polimorfismo no Íntron 4 e -786 juntos. Assim, os objetivos deste trabalho foram: verificar se existe relação entre a prevalência de hipertensão arterial e a presença do polimorfismo para o gene da eNOS nas duas posições - 786 e Íntron 4, separadamente e juntamente, em voluntários acima de 40 anos e também avaliar se existe relação entre o nível de atividade física e os valores de pressão arterial em indivíduos com e sem estes polimorfismos. Para a análise genética foram feitas análises de reação em cadeia da polimerase (PCR) e para a classificação dos níveis de atividade...(Resumo completo, clicar acesso eletrônico abaixo)

The PI3K-Akt-eNOS pathway is involved in aortic hyporeactivity to Phenylephrine associated with late pregnancy in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Insights into HLA-G genetics provided by worldwide haplotype diversity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene is associated with decreased NO production in a mercury-exposed population

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a potent vasodilator and plays a prominent role in regulating the cardiovascular system. Decreased basal NO release may predispose to cardiovascular diseases. Evidence suggests that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene may regulate eNOS expression. On the other hand, some recent reports strongly suggest an association between methylmercury (MeHg) exposures and altered NO synthesis. In the present study, we investigate the contribution of the 27-pb tandem repeat polymorphism on nitric oxide production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population. Two-hundred-two participants (98 men and 104 women), all chronically exposed to MeHg through fish consumption were examined. Mean blood Hg concentration and nitrite plasma concentration were 50.5 +/- 35.4 mu g/L and 251.4 +/- 106.3 nM, respectively. Mean systolic and diastolic blood pressure were 120.1 +/- 19.4 mm Hg and 72.0 +/- 10.6 mm Hg, respectively. Mean body mass index was 24.5 +/- 4.3 kg/m(2) and the mean heart rate was 69.8 +/- 11.8 bpm. There were no significant differences in age, arterial blood pressure, body mass index or cardiac frequency between genotype groups (all P>0.05). However, we observed different nitrite concentrations in the genotypes groups, with lower nitrite levels for the 4a4a genotype carriers. Age, gender and the presence of intron 4 polymorphism contributed to nitrite reduction as a result of blood Hg concentration. Taken together, our results show that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene increases susceptibility to cardiovascular diseases after MeHg exposure by modulating nitric oxide levels. (C) 2011 Elsevier B.V. All rights reserved.

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib

Background: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bio-availability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs. Aim: To investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML Methods: One hundred eighteen CML patients initially treated with a standard dose of IM (400 mg/day) for 18 months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A (rs2032582) were evaluated by PCR-RFLP. Results: ABCB1 polymorphisms were not related with a risk for CML in this sample population (p<0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p>0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p = 0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p = 0.022). Conclusions: The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients. (C) 2011 Elsevier Inc. All rights reserved.

Serum from Calorie-Restricted Rats Activates Vascular Cell eNOS through Enhanced Insulin Signaling Mediated by Adiponectin

eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high quantities in CR serum) completely prevented the increment in nitrite release and eNOS activation. Overall, we demonstrate that adiponectin in the serum from CR animals increases NO center dot signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR.

Specific matrix metalloproteinase 9 (MMP-9) haplotype affect the circulating MMP-9 levels in women with migraine

We investigated whether three relevant polymorphisms (C-1562T, microsatellite - 90(CA)(14-24), and Q279R) in the MMP-9 gene, or MMP-9 haplotypes, are associated with migraine and affect MMP-9 and tissue inhibitor of MMPs (TIMP)-1 levels in patients with migraine. We studied 102 healthy women (controls) and 187 women with migraine (141 without aura - MWA, and 46 with aura - MA). Patients with MWA had higher plasma MMP-9 concentrations than patients with MA. Patients with MA had the highest TIMP-1 and lowest MMP-9/TIMP-1 ratios. The MMP-9 "C L Q" haplotype was associated with higher plasma MMP-9 concentrations in migraine patients. (C) 2012 Elsevier B.V. All rights reserved.

Inducible nitric oxide synthase haplotype associated with migraine and aura

Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive NO amounts possibly contributing to migraine are derived from increased expression and activity of inducible NO synthase (iNOS). We tested the hypothesis that two functional, clinically relevant iNOS genetic polymorphisms (C-1026 A-rs2779249 and G2087A-rs2297518) are associated with migraine with or without aura. We studied 142 healthy women without migraine (control group) and 200 women with migraine divided into two groups: 148 with migraine without aura (MWA) and 52 with aura (MA). Genotypes were determined by real-time polymerase chain reaction using the Taqman (R) allele discrimination assays. The PHASE 2.1 software was used to estimate the haplotypes. The A allele for the G2087A polymorphism was more commonly found in the MA group than in the MWA group (28 vs. 18%; P < 0.05). No other significant differences in the alleles or genotypes distributions were found (P > 0.05). The haplotype combining both A alleles for the two polymorphisms was more commonly found in the MA group than in the control group or in the MWA group (19 vs. 10 or 8%; P = 0.0245 or 0.0027, respectively). Our findings indicate that the G2087A and the C-1026 A polymorphism in the iNOS gene affect the susceptibility to migraine with aura when their effects are combined within haplotypes, whereas the G2087A affects the susceptibility to aura in migraine patients. These finding may have therapeutic implications when examining the effects of selective iNOS inhibitors.