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1.
Cytokine ; 113: 177-184, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30539779

RESUMO

Asthma and allergy affect hundreds of millions of people from childhood to old age. In most of them, the inflammatory process of respiratory allergies involves the participation of type 2 cytokines, derived from T helper-2 (Th2)-cell, and Group 2 Innate Lymphoid (ILC2) Cells. An efficient memory Th2 cell response is dependent on IL-13 produced by ILC2s, causing allergic lung inflammation and elevated serum levels of immunoglobulin E. ILC2 cells are derived from common lymphoid progenitors and their growing depends on the transcription factor RORA. The aim of this work was to identify genetic variants in RORA associated with asthma phenotypes and allergy markers. Genomic DNA samples of 1246 individuals participating from Social Changes Asthma and Allergy in Latin America Program (SCAALA) have been genotyped using Illumina Human 2.5 Omni Beadchip. Logistics regressions have been performed to analyze the association among RORA variants and asthma, skin prick tests (SPT), specific IgE and type 2 cytokine production. Twelve single nucleotide variants (SNVs) were significantly associated with atopy (P < 0.01), in which four of them, rs10162630, rs17191519, rs17270243, and rs55796775 and their haplotypes were strongly and positively associated (P < 0.001). Furthermore, these variants increased the RORA gene expression in silico analysis. Other SNVs in RORA were associated with allergy markers, atopic and non-atopic asthma. Therefore, it is believed that variants in RORA gene may influence immunologic features of asthma and allergies and could be possible targets for future treatment of allergic diseases.


Assuntos
Asma/genética , Predisposição Genética para Doença/genética , Hipersensibilidade/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Biomarcadores/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Citocinas/genética , Feminino , Genótipo , Humanos , Imunidade Inata/genética , Imunoglobulina E/sangue , Imunoglobulina E/genética , Inflamação/genética , Interleucina-13/genética , Pulmão/metabolismo , Masculino , Células Th2/metabolismo
2.
Rev Paul Pediatr ; 40: e2021030, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35703718

RESUMO

OBJECTIVE: The aim of this study was to compare the anthropometric, biochemical, and hormonal characteristics and the presence of genetic polymorphisms of leptin, adiponectin, and tumor necrosis factor alpha (TNF-α) between eutrophic and obese children and adolescents. METHODS: This is a case-control study involving 104 children and adolescents. All subjects were assessed for anthropometric characteristics and clinical, laboratory, and genetic polymorphism parameters. The sample was selected from the pediatric endocrinology outpatient clinic specialized in the treatment of obesity in children and adolescents according to the Centers for Disease Control and Prevention (CDC) classification, and controls were selected from the same location in the general pediatric outpatient clinic. RESULTS: As a result, the parameters, such as black color, obese parents, hypertensive parents, and early weaning, were found to be associated with obesity. Increased levels of insulin, triglyceride, total cholesterol, LDL cholesterol, CRP-U, AST, ALT, GGT, free T4, IGF-1, and uric acid and low levels of HDL cholesterol are found to be associated with a higher chance of obesity. The presence of AG/AA polymorphisms in the leptin is associated with a 290% (OR 3.9) higher chance of obesity, and for adiponectin genes, the chances are 740% (OR 8.4) higher. In these obese children and adolescents with AG/AA haplotypes, serum leptin levels were increased and adiponectin levels were decreased in eutrophic individuals, whereas serum TNF-α levels did not change. CONCLUSIONS: The AG/AA polymorphisms in the leptin and adiponectin genes alter the serum levels of these adipokines and predispose them to obesity, and many anthropometric, biochemical, and hormonal markers are altered, demonstrating early consequences for the health of these obese children and adolescents.


Assuntos
Leptina , Obesidade Infantil , Adiponectina/genética , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Humanos , Leptina/genética , Obesidade Infantil/genética , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética
3.
Artigo em Inglês | MEDLINE | ID: mdl-32834827

RESUMO

BACKGROUND: Vitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control. Our objective was to investigate associations between variants in genes of vitamin D pathway with serum levels of 25-hydroxyvitamin D (25(OH)D), atopy, asthma and asthma severity in teenagers from Northeast Brazil. METHODS: This is a cross sectional study nested in a cohort population of asthma. 25(OH)D was quantified from 968 of 11-17 years old individuals by ELISA. Asthma diagnosis was obtained by using the ISAAC Phase III questionnaire. Specific IgE was determined by ImmunoCAP; genotyping was performed using the 2.5 HumanOmni Biochip from Illumina. Statistical analyses were performed in PLINK 1.07 and SPSS 22.1. RESULTS: After quality control, 104 Single Nucleotides Variants (SNVs) in vitamin D pathway genes, typed in 792 individuals, were included in the analysis. The allele A of rs10875694 on VDR was positively associated with atopy (OR = 1.35; 95% CI 1.01-1.81). The allele C of rs9279 on VDR, was negatively associated with asthma risk (OR = 0.66; 95% CI 0.45-0.97), vitamin D insufficiency (OR = 0.78; 95% CI 0.70-0.96) and higher VDR expression. Two variants in VDR were associated with asthma severity, the allele A of rs2189480 (OR = 0.34; 95% CI 0.13-0.89) and the allele G of rs4328262 (OR = 3.18; 95% CI 1.09-9.28). The combination of variants in CYP2R1 and CYP24A1 (GAC, to rs10500804, rs12794714 and rs3886163, respectively) was negatively associated with vitamin D production (ß = - 1.24; 95% CI - 2.42 to - 0.06). CONCLUSIONS: Genetic variants in the vitamin D pathway affect vitamin D serum levels and, thus, atopy and asthma.

4.
Rev. baiana saúde pública ; 47(1): 210-226, 20230619.
Artigo em Português | LILACS | ID: biblio-1438358

RESUMO

A vacina constitui um dos principais métodos de prevenção contra doenças. Em 1973, o Brasil criou o Programa Nacional de Imunizações a fim de promover a imunização gratuita para a população, o que mais tarde tornou o país em referência mundial em vacinação. No entanto, a recusa vacinal ainda é um grande problema de saúde pública, sendo o movimento antivacina um dos destaques dessa realidade. Dessa forma, o objetivo deste artigo é avaliar como o movimento antivacina impacta na saúde pública no Brasil através da diminuição da cobertura vacinal. Trata-se de uma pesquisa de metodologia mista, com uma primeira etapa qualitativa, composta de uma revisão integrativa nas plataformas PubMed, LILACS e SciELO, no período de 2010 a 2020, e uma pesquisa documental em portais de movimentos antivacina; e uma segunda etapa quantitativa, em que foi realizado um estudo epidemiológico do tipo ecológico, com consulta nas bases eletrônicas do Datasus e no Sistema de Informações do Programa Nacional de Imunizações (SI-PNI), no período de 2010 a 2022. No período investigado, apenas em 2015 o Brasil alcançou a meta preconizada de cobertura vacinal, diferentemente dos anos seguintes, que apresentaram oscilações preocupantes. As publicações apresentam argumentos utilizados pelos grupos antivacina, evidenciados entre 2015 e 2019, período em que os dados de cobertura vacinal oscilaram. Assim, conclui-se que a ascensão do movimento antivacina é um dos fatores que influenciaram na queda da vacinação no Brasil, a exemplo do sarampo e da febre amarela.


The vaccine is one of the main methods of preventing diseases. Since 1973, Brazil created the National Immunization Program to ensure free immunization to the population, which later made the country a world reference in vaccination. However, vaccine refusal is still a great public health issue, and the anti-vaccine movement stand out in this reality. Thus, the purpose of this article is to evaluate how the anti-vaccine movement affects public health in Brazil with vaccination coverage reduction. This is a mixed methodology study, with first a qualitative step, composed of an integrative review in the platforms PubMed, LILACS, and SciELO, in the period from 2010 to 2020,and a documental research in portals of anti-vaccination movements; and a second quantitative step, where an epidemiological study of the ecological type was carried out, with consultation in the electronic databases of DATASUS and in the Information System of the National Immunization Program (SI-PNI) in the period of 2010 to 2022. In the investigative period, only in 2015 Brazil managed to reach the recommended vaccination coverage goal, unlike in the following years, which showed worrying fluctuations. The publications summarize arguments used by the anti-vaccination groups, evidenced between 2015 and 2019, a period in which the vaccination coverage data fluctuated. Therefore, it is clear that the rise of the anti-vaccination movement is a factor that influenced the drop in vaccination numbers in Brazil, with yellow fever and measles as examples.


La vacuna es uno de los principales métodos de prevención de enfermedades. En 1973, Brasil creó el Programa Nacional de Inmunización con el fin de promover la inmunización gratuita para la población, lo que luego convirtió al país en un referente mundial en vacunación. Sin embargo, la negativa de la vacuna sigue siendo un problema importante en la salud pública, y el movimiento antivacunas es uno de los aspectos más destacados de esta realidad. Así, el objetivo de este artículo es evaluar cómo el movimiento antivacunas impacta en la salud pública en Brasil mediante la disminución de la cobertura de vacunación. Se trata de un estudio epidemiológico mixto, con una primera etapa cualitativa, consistente en una revisión integradora en las plataformas PubMed, Lilacs y SciELO, en el período de 2010 a 2020, y una investigación documental en portales de movimientos antivacunas; y una segunda etapa cuantitativa, en la que se realizó un estudio epidemiológico de tipo ecológico, con consulta en las bases de datos electrónicas de DATASUS y en el Sistema de Información del Programa Nacional de Inmunización (SI-PNI), en el período de 2010 a 2022. Entre eses años, solo el año 2015 logró alcanzar la meta recomendada, a diferencia de los años siguientes, que mostraron fluctuaciones preocupantes en la cobertura de vacunación. Las publicaciones mostraron los argumentos utilizados por los grupos antivacina, evidenciados entre 2015 y 2019, período en que los datos de cobertura de la vacuna fluctuaron. Así, se concluye que la asunción del movimiento antivacunación es uno de los factores que influye en la caída de la vacunación en Brasil, como en el sarampión y la fiebre amarilla.


Assuntos
Humanos , Cobertura Vacinal/estatística & dados numéricos
5.
Mol Immunol ; 101: 294-302, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30032071

RESUMO

Atopic asthma, which is characterized by the chronic inflammation and morbidity of airways, is a disease of great complexity, and multiple genetic and environmental factors are involved in its etiology. In the first genome-wide association study (GWAS) conducted in Brazil for asthma, a positive association was found between atopic asthma and a variant (rs1999071), which is located between the DAD1 and OXA1L genes, although neither gene has previously been reported to be associated with asthma or allergies. The DAD1 gene is involved in the regulation of programmed cell death, and OXA1L is involved in biogenesis and mitochondrial oxidative phosphorylation. This study aimed to evaluate how polymorphisms in DAD1 and OXA1L are associated with asthma and markers of atopy in individuals from the Salvador cohort of the SCAALA (Social Change Asthma and Allergy in Latin America) program. The DNA of 1220 individuals was genotyped using the Illumina 2.5 Human Omni Bead chip. Logistic regression analyses were performed with PLINK 1.9 software to verify the association between DAD1 and OXA1L polymorphisms and asthma and atopic markers, adjusted for sex, age, helminth infections and ancestry markers, using an additive model. The DAD1 and OXA1L genes were associated with some of the evaluated phenotypes, such as asthma, skin prick test (SPT), specific IgE for aeroallergens, and Th1/Th2-type cytokine production. Using qPCR, as well as in silico gene expression analysis, we have demonstrated that some of the polymorphisms in both genes are able to affect their respective gene expression levels. In addition, DAD1 was over-expressed in asthmatic patients when compared with controls. Thus, our findings demonstrate that variants in both the DAD1 and OXA1L genes may affect atopy and asthma in a Latin American population with a high prevalence of asthma.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Asma/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Predisposição Genética para Doença , Hipersensibilidade Imediata/genética , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único/genética , Asma/sangue , Brasil , Estudos de Casos e Controles , Criança , Pré-Escolar , Simulação por Computador , Complexo IV da Cadeia de Transporte de Elétrons/sangue , Feminino , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Hipersensibilidade Imediata/sangue , Desequilíbrio de Ligação/genética , Masculino , Proteínas Mitocondriais/sangue , Modelos Biológicos , Proteínas Nucleares/sangue , Fatores de Risco
6.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 40: e2021030, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1387505

RESUMO

ABSTRACT Objective: The aim of this study was to compare the anthropometric, biochemical, and hormonal characteristics and the presence of genetic polymorphisms of leptin, adiponectin, and tumor necrosis factor alpha (TNF-α) between eutrophic and obese children and adolescents. Methods: This is a case-control study involving 104 children and adolescents. All subjects were assessed for anthropometric characteristics and clinical, laboratory, and genetic polymorphism parameters. The sample was selected from the pediatric endocrinology outpatient clinic specialized in the treatment of obesity in children and adolescents according to the Centers for Disease Control and Prevention (CDC) classification, and controls were selected from the same location in the general pediatric outpatient clinic. Results: As a result, the parameters, such as black color, obese parents, hypertensive parents, and early weaning, were found to be associated with obesity. Increased levels of insulin, triglyceride, total cholesterol, LDL cholesterol, CRP-U, AST, ALT, GGT, free T4, IGF-1, and uric acid and low levels of HDL cholesterol are found to be associated with a higher chance of obesity. The presence of AG/AA polymorphisms in the leptin is associated with a 290% (OR 3.9) higher chance of obesity, and for adiponectin genes, the chances are 740% (OR 8.4) higher. In these obese children and adolescents with AG/AA haplotypes, serum leptin levels were increased and adiponectin levels were decreased in eutrophic individuals, whereas serum TNF-α levels did not change. Conclusions: The AG/AA polymorphisms in the leptin and adiponectin genes alter the serum levels of these adipokines and predispose them to obesity, and many anthropometric, biochemical, and hormonal markers are altered, demonstrating early consequences for the health of these obese children and adolescents.


RESUMO Objetivo: Comparar as características antropométricas, bioquímicas, hormonais e a presença de polimorfismos genéticos de leptina, adiponectina e fator de necrose tumoral alfa (TNF-α) entre crianças e adolescentes eutróficos e obesos. Métodos: Trata-se de um estudo caso-controle conduzido com 104 crianças e adolescentes. Todos os indivíduos foram avaliados quanto às características antropométricas e parâmetros clínicos, laboratoriais e de polimorfismo genético. A amostra foi selecionada no ambulatório de endocrinologia pediátrica especializado no tratamento da obesidade em crianças e adolescentes de acordo com a classificação do Centers for Disease Control and Prevention (CDC), e os controles foram selecionados no mesmo local, porém no ambulatório de pediatria geral. Resultados: Alguns parâmetros foram associados à obesidade em nosso estudo: cor preta, pais obesos, pais hipertensos e desmame precoce. Níveis aumentados de insulina, triglicerídeos, colesterol total, colesterol LDL, PCR-U, AST, ALT, GGT, T4 Livre, IGF-1, ácido úrico e níveis baixos de colesterol HDL estão associados a uma chance maior de obesidade. A presença de polimorfismos AG/AA na leptina está associada a uma chance 290% (OR 3,9) maior de obesidade, enquanto para os genes da adiponectina as chances são 740% (OR 8,4) maiores. Nessas crianças e adolescentes obesos com haplótipos AG/AA, os níveis séricos de leptina aumentaram e os níveis de adiponectina diminuíram em relação aos eutróficos, já os níveis séricos de TNF-α não se alteraram. Conclusões: Concluiu-se que os polimorfismos AG/AA nos genes da leptina e adiponectina alteram os níveis séricos dessas adipocinas e predispõem à obesidade precoce, e muitos marcadores antropométricos, bioquímicos e hormonais ficam alterados, trazendo consequências para a saúde dessas crianças e adolescentes.

7.
Asthma Res Pract ; 1: 10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27965764

RESUMO

Multiple factors interact to trigger allergic diseases, including individual genetic background and factors related to the environment such as exposure to allergens, air pollution and respiratory infections. The FOXP3 transcription factor is constitutively expressed in CD4+CD25+FOXP3+ regulatory T cells (Tregs) and is critical for the maintenance of immune homeostasis. For example, FOXP3 is responsible for the suppression of the Th2 response following exposure to allergens. Studies have shown that expression of the FOXP3 gene is reduced in patients with asthma and allergies compared to healthy controls. Therefore, the impairment of FOXP3 function caused by genetic polymorphisms and/or epigenetic mechanisms may be involved in the etiology of asthma and other allergic diseases. This review discusses some aspects of the role of FOXP3 in the development of asthma and allergy, with a particular emphasis on genetic and epigenetic factors.

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