Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension

Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

LEPR p. Q223R, Beta 3-AR p. W64R and LEPc. -2548G>A gene variants in obese Brazilian subjects

Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. The adrenergic receptor ¦Â3 (¦Â3-AR), leptin (LEP) and leptin receptor (LEPR) genes have been intensively evaluated in the search of variants that could be related to obesity and its cardiometabolic complications. The results of most of these studies have been controversial. In the present study, we investigated the relationship of the ¦Â3-AR p.W64R, LEP c.-2548G>A and LEPR p.Q223R gene variants with body mass index (BMI), in Brazilian subjects of different genetic backgrounds and ethnic origins. Two hundred obese patients (60 males, 140 females, BMI ¡Ý 30 kg/m2) were screened and compared to 150 lean healthy subjects (63 males, 87 females, BMI ¡Ü 24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction. Polymerase chain reaction products were digested with specific restriction enzymes and separated by electrophoresis. There was no significant difference in the genotype frequency of the ¦Â3-AR p.W64R and the LEP c.-2548G>A polymorphisms, between lean and obese subjects. However, the genotype and allele frequencies of the LEPR p.Q223R variant were significantly different between the normal weight and obese groups. Haplotype analysis has shown an association between the G/G allelic combination of c.-2548G>A LEP and c.668A>G LEPR, in obese subjects. Our results suggest that genetic variability in the leptin receptor is associated with body weight regulation, the LEPR p.Q223R variant being related to BMI increase. The haplotype combination of LEP c.-2548G>A and LEPR p.Q223R variants was related to a 58% increase in obesity risk.

Considerations on the effect of anti-sandfly antibodies on biological parameters of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae)

A imunização de hospedeiros vertebrados com componentes derivados de vetores pode se constituir numa estratégia alternativa para o controle de doenças transmitidas por insetos. No presente estudo avaliamos o efeito de anticorpos antiflebótomos sobre alguns parâmetros biológicos de fêmeas de Lutzomyia longipalpis, vetor de leishmaniose visceral. Coelhos foram imunizados com extratos de tubos digestivos de fêmeas alimentadas com açúcar (GS), fêmeas alimentadas com sangue (GB), carcaças de fêmeas alimentadas com açúcar (CS) ou carcaças de fêmeas alimentadas com sangue (CB), e coelho imunizado por repetidas picadas de fêmeas de flebótomos (BITE). Os soros imunes de coelhos apresentaram títulos aumentados quando comparados com os soros pré-imunes, e bandas específicas foram detectadas por meio de Western Blot. A análise dos parâmetros biológicos revelou um decréscimo na fecundidade no grupo de fêmeas alimentadas em coelho imunizado com GB e BITE. A longevidade e a mortalidade foram estudadas em fêmeas com postura (paridas) e fêmeas sem postura (nulíparas). Fêmeas nulíparas que se alimentaram em coelho imunizado por repetidas picadas morreram em maior percentual. A análise da mortalidade, após a postura dos ovos, revelou um pico no quinto dia em todos os grupos, mas em fêmeas que se alimentaram em coelho submetido a repetidas picadas, foi antecipada para o terceiro dia.

Personalized diagnosis by cached solutions with hypertension as a study model

Statistical modeling of links between genetic profiles with environmental and clinical data to aid in medical diagnosis is a challenge. Here, we present a computational approach for rapidly selecting important clinical data to assist in medical decisions based on personalized genetic profiles. What could take hours or days of computing is available on-the-fly, making this strategy feasible to implement as a routine without demanding great computing power. The key to rapidly obtaining an optimal/nearly optimal mathematical function that can evaluate the [quot ]disease stage[quot ] by combining information of genetic profiles with personal clinical data is done by querying a precomputed solution database. The database is previously generated by a new hybrid feature selection method that makes use of support vector machines, recursive feature elimination and random sub-space search. Here, to evaluate the method, data from polymorphisms in the renin-angiotensin-aldosterone system genes together with clinical data were obtained from patients with hypertension and control subjects. The disease [quot ]risk[quot ] was determined by classifying the patients' data with a support vector machine model based on the optimized feature; then measuring the Euclidean distance to the hyperplane decision function. Our results showed the association of renin-angiotensin-aldosterone system gene haplotypes with hypertension. The association of polymorphism patterns with different ethnic groups was also tracked by the feature selection process. A demonstration of this method is also available online on the project's web site.

A simple model for the estimation of congenital malformation frequency in racially mixed populations

É proposto um modelo simples, fazendo uso do método da máxima verossimilhança, para estimar as freqüências de malformaçöes em grupos raciais, baseado em dados obtidos em serviços hospitalares. Este modelo usa as proporçöes de mistura racial e a freqüência observada da malformaçäo. O método foi aplicado a dois defeitos: polidactilia pós-axial e lábio leporino, cujas freqüências säo reconhecidamente heterogêneas entre grupos raciais. As estimativas obtidas em cada grupo racial foram as esperadas para estas malformaçöes, o que prova a aplicabilidade do método.

On the association between HLA-A1 and B5 and clinical forms of schistosomiasis mansoni

The association between both HLA-A1 and B5 antigens and chronic forms of human schistosomiasis was studied in 64 patients and 26 normal controls from a southern Brazilian hospital. No apparent correlation between the chronic forms of the disease and the expression of those antigens was detected. However, the analysis of these date together with those observed on an Egyptian sample suggests that the presence of either of the antigens and the hepatomegalic forms of schistosomiasis is significant, without heterogeneity. Converseley, the association of histocompatibility antigens with splenogegaly is consistent and significant only for HLA-B5, but not HLA-A1

ABO segregation analysis of sib-pairs in two Brazilian samples

Com o objetivo de testar as discrepâncias observadas na segregaçäo dos grupos sanguineos ABO entre pares consecutivos de irmäos, como foi sugerido por Cifuentes and Valenzuela (1986) em uma populaçäo chilena, foram analisadas duas amostras brasileiras, cada uma com cerca de 1000 pares de irmäos. Os resultados mostram claramente a inexistência de diferenças significativas tanto nas amostras totais como nas subdividas de acordo com os fenótipos maternos, näo permitindo, portanto, a generalizaçäo dos resultados chilenos. As observaçöes agrupadas, das amostras brasileiras e a chilena näo apoiam a hipótese da existência de um mecanismo de "tolerância", postulada por Cirfuentes e Valenzuela. A necessidade de informaçöes completas de famílias nucleares é enfatizada, no sentido de evitar achados inconsistentes