Browsing by Author "Pereira, Alexandre da Costa"

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    BDKRB2 +9/−9 polymorphism Is associated with higher risk for diabetes mellitus in the Brazilian general population.
    (2012) Alvim, Rafael de Oliveira; Santos, Paulo Caleb Júnior de Lima; Nascimento Neto, Raimundo Marques do; Coelho, George Luiz Lins Machado; Mill, José Geraldo; Krieger, José Eduardo; Pereira, Alexandre da Costa
    Some mechanisms have been proposed to explain the role of bradykinin on glucose homeostasis and some studies reported that the BDKRB2 +9/−9 polymorphism was associated to the transcriptional activity of the receptor. In this scenario, the main aim of this study was to evaluate the association of the BDKRB2 +9/−9 polymorphism with diabetes mellitus risk in the Brazilian general population. This study included 1,032 subjects of the general urban population. Anthropometrical, blood pressure, biochemical, and genotype analyses for the BDKRB2 +9/−9 bp insertion/deletion polymorphism were performed. Individuals carrying +9/+9 or +9/−9 genotypes had higher glucose values (84.5mg/dL versus 80.6mg/dL, resp.) and higher frequency of diabetes mellitus (7.6% versus 3.6%, resp.) compared to individuals carrying −9/−9, adjusting for age and gender. In addition, higher diabetes mellitus risk was associated to presence of the +9/+9 or +9/−9 genotypes (OR= 1.91; 95% CI = 1.09–4.19; P = 0.03). Our data suggest that the BDKRB2 +9/-9 polymorphismmay act as a geneticmodulator of glucose homeostasis. It was previously associated to insulin sensitivity, glucose uptake, and insulin secretion, and, in this study, data suggest that the polymorphism may increase susceptibility to chronic metabolic conditions such as diabetes in the Brazilian population.
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    CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population.
    (2011) Santos, Paulo Caleb Júnior de Lima; Soares, Renata A. G.; Santos, Diogo B. G.; Nascimento Neto, Raimundo Marques do; Coelho, George Luiz Lins Machado; Nicolau, José Carlos; Mill, José Geraldo; Krieger, José Eduardo; Pereira, Alexandre da Costa
    Background: Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population. Methods: One hundred and eighty three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the ABCB1c.C3435T (rs1045642), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*4 (rs28399504), CYP2C19*5 (rs56337013), and CYP2C19*17 (rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The CYP2C19*3, CYP2C19*4 and CYP2C19*5 variants were genotyped in a subsample of subjects (300 samples randomly selected). Results: The CYP2C19*3 and CYP2C19*5 variant alleles were not detected and the CYP2C19*4 variant allele presented a frequency of 0.3%. The allelic frequencies for the ABCB1c.C3435T, CYP2C19*2 and CYP2C19*17 polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population. Conclusion: Our findings indicate the existence of inter-ethnic differences in the ABCB1 and CYP2C19 variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more costeffective programs towards individualization of clopidogrel therapy.
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    Derivation and external validation of a simple prediction model for the diagnosis of type 2 Diabetes Mellitus in the Brazilian urban population.
    (2009) Sousa, André Gustavo Pires de; Pereira, Alexandre da Costa; Marquezine, Guilherme Figueiredo; Nascimento Neto, Raimundo Marques do; Freitas, Silvia Nascimento de; Nicolato, Roney Luiz de Carvalho; Coelho, George Luiz Lins Machado; Rodrigues, Sérgio Lamego; Mill, José Geraldo; Krieger, José Eduardo
    A risk score model was developed based in a population of 1,224 individuals from the general population without known diabetes aging 35 years or more from an urban Brazilian population sample in order to select individuals who should be screened in subsequent testing and improve the efficacy of public health assurance. External validation was performed in a second, independent, population from a different city ascertained through a similar epidemiological protocol. The risk score was developed by multiple logistic regression and model performance and cutoff values were derived from a receiver operating characteristic curve. Model’s capacity of predicting fasting blood glucose levels was tested analyzing data from a 5-year follow-up protocol conducted in the general population. Items independently and significantly associated with diabetes were age, BMI and known hypertension. Sensitivity, specificity and proportion of further testing necessary for the best cutoff value were 75.9, 66.9 and 37.2%, respectively. External validation confirmed the model’s adequacy (AUC equal to 0.72). Finally, model score was also capable of predicting fasting blood glucose progression in non-diabetic individuals in a 5-year follow-up period. In conclusion, this simple diabetes risk score was able to identify individuals with an increased likelihood of having diabetes and it can be used to stratify subpopulations in which performing of subsequent tests is necessary and probably cost-effective.
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    Lipoprotein(a) as a risk factor associated with ischemic heart disease : Ouro Preto Study.
    (2007) Cândido, Ana Paula Carlos; Ferreira, Silvania; Lima, Angélica Alves; Nicolato, Roney Luiz de Carvalho; Freitas, Silvia Nascimento de; Brandão, Paulo; Pereira, Alexandre da Costa; Krieger, José Eduardo; Nascimento Neto, Raimundo Marques do; Coelho, George Luiz Lins Machado
    Evidences suggest that lipoprotein(a) [Lp(a)] is an important risk factor for cardiovascular disease. However, literature has been controversial in confirming its role as an independent risk factor for cardiovascular disease. The objective of the present study is to evaluate the association between serum levels of Lp(a) and ischemic heart disease as well as other cardiovascular risk factors in a population-based study conducted on a local cohort of the Brazilian population. Lp(a) serum levels were measured in 400 individuals selected from a larger sample of a populational survey carried out in Ouro Preto, a city in the southeast of Brazil. Lipid profile, fasting blood glucose, anthropometric and clinical parameters were analyzed. Lp(a) levels were significantly associated with the presence of ischemic heart disease. In relation to other cardiovascular risk factors, it was verified that Lp(a) levels were statistically associated with age, total cholesterol, LDL-cholesterol and percentage of body fat determined by bioelectric impedance. Lp(a) was also highly associated with the Framingham risk score (p = 0.003). In a multivariate analysis two significant interactions were revealed; one involving ischemic heart disease, sex and age and other associating ischemic heart disease, age and total cholesterol. In summary, in the present analysis Lp(a) serum levels were correlated with the occurrence of ischemic heart disease and other cardiovascular risk factors.
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    Prevalência e fatores de risco associados à doença arterial periférica no Projeto Corações do Brasil.
    (2008) Makdisse, Marcia; Pereira, Alexandre da Costa; Brasil, David Pádua; Borges, Jairo Lins; Coelho, George Luiz Lins Machado; Krieger, José Eduardo; Nascimento Neto, Raimundo Marques do; Chagas, Antonio Carlos Palandri
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    Projeto corações do Brasil.
    (2005) Nascimento Neto, Raimundo Marques do; Krieger, José Eduardo; Coelho, George Luiz Lins Machado; Pereira, Alexandre da Costa
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    Self-declared ethnicity associated with risk factors of cardiovascular diseases in an urban sample of the Brazilian population: the role of educational status in the association.
    (2013) Santos, Hadassa Campos; Fragoso, Tiago de Miranda; Coelho, George Luiz Lins Machado; Nascimento Neto, Raimundo Marques do; Mill, José Geraldo; Krieger, José Eduardo; Pereira, Alexandre da Costa
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    SLCO1B1 RS4149056 polymorphism associated with statin-induced myopathy is differently distributed according to ethnicity in the Brazilian general population : amerindians as a high risk ethnic group.
    (2011) Santos, Paulo Caleb Júnior de Lima; Soares, Renata A. G.; Nascimento Neto, Raimundo Marques do; Coelho, George Luiz Lins Machado; Mill, José Geraldo; Krieger, José Eduardo; Pereira, Alexandre da Costa
    Background: Recent studies reported the association between SLCO1B1 polymorphisms and the development of statin-induced myopathy. In the scenario of the Brazilian population, being one of the most heterogeneous in the world, the main aim here was to evaluate SLCO1B1 polymorphisms according to ethnic groups as an initial step for future pharmacogenetic studies. Methods: One hundred and eighty-two Amerindians plus 1,032 subjects from the general urban population were included. Genotypes for the SLCO1B1 rs4149056 (c.T521C, p.V174A, exon 5) and SLCO1B1 rs4363657 (g.T89595C, intron 11) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis with the Rotor Gene 6000® instrument. Results: The frequencies of the SLCO1B1 rs4149056 and rs4363657 C variant allele were higher in Amerindians (28.3% and 26.1%) and were lower in African descent subjects (5.7% and 10.8%) compared with Mulatto (14.9% and 18.2%) and Caucasian descent (14.8% and 15.4%) ethnic groups (p < 0.001 and p < 0.001, respectively). Linkage disequilibrium analysis show that these variant alleles are in different linkage disequilibrium patterns depending on the ethnic origin. Conclusion: Our findings indicate interethnic differences for the SLCO1B1 rs4149056 C risk allele frequency among Brazilians. These data will be useful in the development of effective programs for stratifying individuals regarding adherence, efficacy and choice of statin-type.