BackgroundAsthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population.Methods1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1 877 526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples.ResultsTwo chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95 % CI 1.45–2.18, p-value 2.83 × 10−8) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95 % CI 2.02–4.49, p-value 6.68 × 10−8 and rs8029377, MAF 0.03, OR 2.49, 95 % CI 1.76–3.53, p-value 2.45 × 10−7). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples.ConclusionsWe conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0296-7) contains supplementary material, which is available to authorized users.
R E S U M OOs processos que promovem alterações em variáveis limnológicas são amplos e necessitam de estudos que considerem as peculiaridades das bacias de contribuição, bem como o uso e cobertura de suas áreas. O presente artigo teve por objetivo comparar a dinâmica de parâmetros limnológicos da Represa Dr. João Penido -Juiz de Fora/MG em diferentes regimes pluviométricos, além de compreender os mecanismos atuantes na variação dos mesmos. O teste t de Student verificou a ocorrência de variação sazonal significativa para os parâmetros: cor, turbidez, ferro, condutividade e demanda bioquímica de oxigênio. Através da Análise Fatorial/Análise de Componentes Principais foi excluída a variável pH por não contribuir para a variância total dos dados além de destacar, dentre as variáveis estudadas, as que mais influenciaram na qualidade da água. Foram utilizadas as quatro primeiras componentes que explicaram 71% da variância total dos dados indicando o escoamento superficial como determinante das variáveis da primeira e da segunda componentes; a contribuição orgânica não associada à precipitação, como sugestiva das variáveis da terceira componente e a dinâmica funcional intrínseca do ambiente aquático como indicativa da quarta componente.Changes in limnological variables of water reservoir in Juiz de Fora due to land use A B S T R A C TThe processes that promote changes in limnological variables are large and require studies that consider the peculiarities of the basins of contribution, as well as the use and coverage of their areas. This article aimed to compare the dynamics of limnological parameters of Dr. Joao Penido reservoir in Juiz de Fora -State of Minas Gerais in different rainfall regimes, as well as understanding the active mechanisms in the variation of the same ones. Student's t-test has revealed the occurrence of significant seasonal variation for the parameters: color, turbidity, iron, electrical conductivity and biochemical oxygen demand. Through factor analysis/principal components analysis variable pH was excluded for not contributing to the variance of all data, highlighting among the studied variables, which contributed more to influence water quality. The first four components were used which explained 71% of the total variance of the data, indicating the runoff as a determinant of the variables of the first and second components; the organic contribution, not associated with the precipitation, as suggestive of the variables of the third component; and intrinsic functional dynamics of the aquatic environment as indicative of the fourth component.Alterações em variáveis limnológicas de manancial de Juiz de Fora devido ao uso da terra
Accumulated evidence supports the contribution of genetic factors in modulating airway function, especially ancestry. We investigated whether genetic polymorphisms can affect lung function in a mixed Brazilian child population using the admixture mapping strategy through RFMix software version 1.5.4 (Stanford University, Stanford, CA, USA), followed by fine mapping, to identify regions whereby local African or European ancestry is associated with lung function measured by the forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio, an indicator of airway obstruction. The research cohort included 958 individuals aged 4 to 11 years enrolled in the SCAALA (Social Change, Asthma, Allergy in Latin America) Program. We identified that African ancestry at 17q21.31, 10q22.2, and 2p23.1 regions was associated with lower lung function measured by FEV1/FVC p < 1.9 × 10−4. In contrast, European ancestry at 17q21.31 showed an opposite effect. Fine mapping pointed out 5 single nucleotide polymorphisms (SNPs) also associated in our replication cohort (rs10999948, rs373831475, rs8068257, rs6744555, and rs1520322). Our results suggest that genomic regions associated with ancestry may contribute to differences in lung function measurements in African American children in Brazil replicated in a cohort of Brazilian adults. The analysis strategy used in this work is especially important for phenotypes, such as lung function, which has considerable disparities in terms of measurements across different populations.
Atopic asthma is a chronic lung disease of lower airways caused mainly due to action of T-helper (Th) 2 type cytokines, eosinophilic inflammation, mucus hypersecretion and airway remodelling. Interleukin (IL)-33 increases type 2 immunity polarization in airway playing critical role in eosinophilic asthma. On the other hand, NLRP3 inflammasome activation results in the release of caspase-1 (Casp-1) which, in its turn, promotes IL-33 inactivation. Recent studies have shown associations between NLRP3 variants and inflammatory diseases. However, no study with genes in NLRP3 inflammassome route has been conducted so far with asthma and atopy in any population to date. Blood samples were collected from 1246 asthmatic and non-asthmatic children. Associations were tested for single nucleotide polymorphism (SNP)s in NLRP3 and CASP1 with asthma and markers of atopy and in cultures stimulated with Blomia tropicalis (Bt) mite crude extract. The T allele of rs4925648 ( NLRP3) was associated with increased asthma risk (OR 1.50, P = 0.005). In addition, the T allele of rs12130711 polymorphism, whithin the same gene, acted as a protector factor for asthma (OR 0.78, P = 0.038). On the other hand, the C allele of rs4378247 NLRP3 variant was associated with lower levels of IL-13 production when peripheral blood cells were stimulated with Bt (OR 0.39, P = 4E-04). In addition, the greater the number of risk alleles in IL33 / NLRP3 / CASP1 route the greater was the risk for asthma. The T allele of rs7925706 CASP1 variant was also associated with increased risk for asthma (OR 1.47, P = 0.008). In addition, this same allele increased the eosinophil counts in blood (mm3) in asthmatic individuals compared with non-asthmatic (P = 0.0004). These results suggest that NLRP3 and CASP1 polymorphisms may be associated with susceptibility for asthma and markers of atopy in our population.
Background: Genetic variants underlying African ancestry have been suggested be implicated in the ethnic-racial inequalities reported for asthma and allergies.Objectives: To investigate the association between individual African ancestry and asthma symptoms, atopic and non-atopic asthma, and atopy in children. Methods:A cross-sectional study encompassing 1190 individuals was conducted.African biogeographic ancestry was estimated using 370 539 genome-wide SNPs.Serum levels of specific IgE were measured, and skin prick test (SPT) performed for the most common local aeroallergens. Information on asthma symptoms was obtained by applying the International Study of Allergy and Asthma in Childhood questionnaire. The associations between the proportion of individual African ancestry and the outcomes investigated were analyzed through multivariate models adjusted for socio-environmental variables, infections markers, and psychosocial factors.Results: Each 20% increase in the proportion of African ancestry was negatively associated with SPT reactivity (OR: 0.79, 95%CI: 0.66-0.96) and positively associated with asthma symptoms in non-atopic individuals (OR: 1.40, 95%CI: 1.03-1.89). We estimated that socioeconomic status and number of infections mediated 28.4% of the effect of African ancestry on SPT reactivity, while 20.2% of the effect on Pediatric Pulmonology. 2019;54:125-132.wileyonlinelibrary.com/journal/ppul
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