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Background: Few genome‐wide association studies (GWAS) on Helicobacter pylori infection susceptibility have been conducted for admixed populations from developing countries. Here, we performed a GWAS to identify genetic factors associated with H. pylori serostatus in a cohort of admixed children from a large Latin American urban center. Methods: A cross‐sectional study involving 1161 children from 4 to 11 years old living in poor areas of Salvador, in northeastern Brazil. Logistic regression analysis was performed to detect associations between single‐nucleotide variants (SNVs) and H. pylori seropositivity, assuming an additive genetic model. Enrichment analyses were conducted using the MAGMA v1.10 software. Results: We found 22 SNVs to be suggestively associated (p < 10−5) with H. pylori seropositivity. The most suggestive SNV was the rs77955022 (p = 4.83e‐07) located in an intronic region of EXOC3 at 5p15.33. The second most suggestively associated SNV was rs10914996 (p = 8.97e‐07), located in an intergenic region at 1p34.3. Furthermore, we were able to replicate three SNVs (p < 0.05) in the Study of Health in Pomerania (SHIP) cohort: the rs2339212 and rs4795970, both located at 17q12 near TMEM132E, as well as the rs6595814, an intronic variant of FBN2 at 5q23.3. The enrichment analysis indicated the participation of genes and metabolic pathways related to the regulation of the digestive system and gastric acid secretion in the risk of seropositivity for H. pylori. Conclusions: Additional studies are required to validate these association findings in larger population samples and to get insight into the underlying physiological mechanisms. [ABSTRACT FROM AUTHOR]

Objective To assess the influence of zinc serum status on the prevalence of wheezing in a sample of children and adolescents in Northeastern Brazil. Research methods and procedures This is a cross-sectional study which included 592 students of 6-12 years old, from the public elementary schools of São Francisco do Conde, Bahia, Northeastern Brazil. Report of wheezing in the past 12 months was collected using a questionnaire of the International Study of Asthma and Allergies in Childhood Program (ISAAC) phase III, adapted to Portuguese. The determination of serum Zn levels was performed using a flame atomic absorption spectrometer. Data on anthropometric status, level of physical activity, pubertal development and socioeconomic information, for each participant were obtained. Multivariate logistic regression analyses were used to assess the associations of interest. Results Of the students, 8.6% (95% CI 6.30-10.9) reported having wheezing. The mean (SD) serum zinc level was 114 (22.9 μg/dL). The results of the multiple logistic regression analysis showed, after adjustments, positive and significant association between low serum zinc levels and wheezing. Students categorized as being below the median for serum Zn concentration presented an almost 1.9-fold increase in the wheezing prevalence ratio (OR = 1.9; 95% CI 1.03-3.53). Conclusion The main findings of this study suggest that the level of zinc may influence the risk of wheezing in late childhood on the study population. [ABSTRACT FROM AUTHOR]

Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44–3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus. • Childhood asthma is associated with the 17q21 region in admixed populations. • Both, allergic and non-allergic childhood asthma, are associated with the 17q21 region. • The association of childhood asthma with the 17q21 region is independent of sex or ancestry. • Seropositivity for Herpes zoster virus infection modifier the association of childhood asthma with the 17q21 region [ABSTRACT FROM AUTHOR]

PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Polymorphisms in genes related to the activation and development of regulatory T cells (Tregs), such as FOXP3, may be associated with asthma and atopy development. Additionally, environmental factors such as exposure to infections can modify the effect of these associations. This study evaluated the impact of polymorphisms in the FOXP3 on the risk of asthma and atopy as also gene-environment interactions in these outcomes., Methods: This study included 1,246 children from the SCAALA program, between 4 and 11 years of age. DNA was extracted from peripheral blood and eight SNPs (rs2280883, rs11465476, rs11465472, rs2232368, rs3761549, rs3761548, rs2232365 and rs2294021) were genotyped using the 2.5 HumanOmni Beadchip from Illumina (San Diego, California, USA) or TaqMan qRT-PCR., Results: The rs2232368 (Allele T) was positively associated with asthma symptoms (OR = 1.95, CI = 1.04 to 3.66, p = 0.040) and skin prick test (SPT) reactivity to aeroallergens (OR = 2.31, CI = 1.16 to 4.59, p = 0.017). The rs3761549 (Allele T) was positively associated with SPT reactivity (OR = 1.44, CI = 1.03 to 2.02, p = 0.034). The rs2280883 (Allele C) was negatively associated with specific IgE to aeroallergens (OR = 0.83, CI = 0.70 to 0.99, p = 0.040). Furthermore, the rs2280883 played a protective role in the development of atopy only in individuals seropositive to Epstein-Barr virus (EBV) infection (OR = 0.74, CI = 0.60 to 0.92, p = 0.003 and OR = 0.74; 95% CI = 0.61-0.91, p = 0.007 for SPT and slgE respectively), but not in individuals without EBV infection., Conclusion: Polymorphisms in the FOXP3 gene were associated with the risk of atopy and asthma development in our population. In addition, EBV infection had an effect modifier of the observed association for rs2280883 variant., (Copyright © 2022. Published by Elsevier B.V.)

Background: Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM)., Objectives: To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children., Methods: We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal., Results: Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR: 0.66, CI95%: 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p < 0.001) and adipose tissue (p < 0.001)., Conclusion: These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Toxoplasma gondii (T gondii) infection has been associated with protection against allergy and autoimmune diseases. We investigated the effects of T gondii infection on cytokine and antibody responses in atopic and nonatopic Brazilian subjects. We have measured in whole-blood cultures, Th1 (IFN-γ and IL-12), Th2 (IL-5) and regulatory cytokine IL-10 in blood cells unstimulated and stimulated with pokeweed mitogen or T gondii soluble tachyzoites antigen (STAg) or Dermatophagoides pteronyssinus antigen. A significant negative association was found between high levels of anti-dust mite IgE and T gondii seropositivity (OR = 0.46; 95%CI = 0.25-0.85). STAg stimulation induced a mixed profile of Th1 and Th2 cytokines (IFN-γ, IL-12 and IL-5) in Tg-positive atopic individuals compared with Tg-negative atopic individuals (P < .0001, P = .033 and P = .003, respectively). In contrast, IL-10 production was not different between these groups. No association was found between T gondii infection and asthma. We hypothesized that the protective effect on atopy might be related to the strong Th1 immune response to T gondii found on the seropositive subjects. From our knowledge, this is the first study to investigate the association between atopy and T gondii infection in Brazilian subjects, analysing the cellular immune responses., (© 2019 John Wiley & Sons Ltd.)

Background: Allergic asthma is a complex disorder that results from a combination of genetic and environmental factors. Studies suggest that helminth infections can activate a regulatory network characterized by the production of regulatory cytokines, such as interleukin 10 and transforming growth factor β1 (TGF-β1) and subsequently protect against immune-mediated diseases, such as asthma. On the other hand, TGF-β1 is increased in the lungs of individuals with asthma and may modulate airway inflammation. The role of TGF- β 1 single-nucleotide polymorphisms (SNPs) in allergic disease remains inconclusive., Objective: To evaluate the effects of genetic variations in the TGF-β1 on allergy and helminths infections in children., Methods: We tested for association among 4 TGF-β1 SNPs and allergic asthma, specific IgE, skin prick test result, and IL-10 production in 1,335 Brazilians. In addition, we analyzed the association with markers of helminth infection (parasite burden, anti-Ascaris IgE, and worm specific IgG4). The polymorphisms were genotyped using Taq Man probes., Results: We found an association between rs1800470 (C allele) and atopic wheezing (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.37-0.95) and markers of allergy (OR, 0.41; 95% CI, 0.22-0.79). In contrast, a positive association was observed between the haplotype ACCA and Trichuris trichiura infection (OR, 1.85; P = .003) and Ascaris lumbricoides infection (OR, 2.01; P < .001). This haplotype was also associated with increased IL-10 production (β = 50.7; P < .001)., Conclusion: Individuals with TGF-β1 polymorphisms have an increased susceptibility to helminth infections and a lower risk of developing allergy. These studies suggest that immune modulation of allergic disease results not only from environmental factors but also from genetic susceptibility and IL-10 production., (Copyright © 2017 American College of Allergy, Asthma & Immunology. All rights reserved.)

Background: Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children., Materials and Methods: We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5' nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK., Results: Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR = 1.63; 95% CI = 1.11-2.39), rs3024491 (OR = 1.71; 95% CI = 1.14-2.57), rs1878672 (OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 (OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori., Conclusions: Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer., (© 2014 John Wiley & Sons Ltd.)

Objective: To evaluate the association between food and nutrition insecurity and asthma in children from Latin America., Design: Cross-sectional study., Setting: São Francisco do Conde, Bahia, north-eastern Brazil., Subjects: The study included 1307 children aged 6-12 years from public elementary schools. Asthma symptoms were collected using a questionnaire that was translated and adapted from the International Study of Asthma and Allergies in Childhood, phase III. The diagnosis of asthma was determined based on reports of wheezing in the previous 12 months. The Brazilian Food Insecurity Scale was used to identify food insecurity. We also obtained demographic, socio-economic and anthropometric information for each participant. We used multivariate logistic regression analyses to assess the associations of interest., Results: Of the children surveyed, 10·4% had a history of wheezing and 64·5% had some degree of food and nutrition insecurity. We found a positive dose-response relationship and statistically significant associations of asthma with moderate (OR = 1·71, 95% CI 1·01, 2·89) and severe (OR = 2·51, 95% CI 1·28, 4·93) food and nutrition insecurity., Conclusions: The results show that moderate and severe food and nutrition insecurity are markers of vulnerability to wheezing. It is important to note that the results of studies in this field have potential implications for social policies that promote food security. Further studies to identify the mechanisms involved in the relationship between food and nutrition insecurity and asthma are needed.

Background: Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG₄ production, protecting against allergies., Objective: We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy., Methods: Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti-A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK., Results: Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach., Conclusions: Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases., Competing Interests: of potential conflict of interest: M. L. Barreto has received grants from the Wellcome Trust and the National Research Council–Brazil and is employed by the Federal University of Bahia. P. J. Cooper has received grants from the Wellcome Trust and is employed by the Liverpool School of Tropical Medicine. A. A. Cruz serves on boards for Merck Sharp & Dohme and Roche; has consultant arrangements with Mantecorp; receives grants from GlaxoSmithKline; receives payment for lectures from Merck Sharp & Dohme; has received travel/accommodations/meeting expenses from Merck Sharp & Dohme and Novartis; and has conducted clinical trials for AstraZeneca, Novartis, TAKEDA, Eurofarma, GlaxoSmithKline, and Genentech. L. C. Pontes-de-Carvalho is employed by the Ministry of Health, Brazil. C. Vergara, C. Foster, M. Campbell, and R. A. Mathias are employed by Johns Hopkins University and have received grants from the National Institutes of Health. K. C. Barnes serves on boards for Genentech; has consultant arrangements with Sanofi-Aventis and Sirius Genomics; is employed by Johns Hopkins University; has received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute; has received payment for lectures from the “Evolution and Diseases of Modern Environments” Symposium, the Cincinnati Children’s Hospital Medical Center Allergy Conference, the 50th Annual Swineford Allergy Conference, and the American Academy of Allergy, Asthma & Immunology; and receives royalties from Up-To-Date. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objective: To evaluate the relative importance of body mass index (BMI) and abdominal obesity in the prevalence of wheezing in Brazilian children., Materials and Methods: This is a cross-sectional study of male and female students, 6-12 years old, from the public elementary schools of São Francisco do Conde, Bahia, Northeast Brazil. Reports of wheezing in the past 12 months were collected using a questionnaire from the International Study of Asthma and Allergies in Childhood Program (ISAAC) phase III, adapted to Portuguese. Anthropometric, demographic, and socioeconomic information was collected. Multivariate logistic regression analyses were used to assess the associations of interest., Results: Of the children surveyed, 10.6% reported wheezing. Excess weight was observed in 16.2%, 10.5%, and 7.9% of the sample, measured by BMI, waist circumference (WC), and the waist-to-height ratio (WHtR), respectively. The percentage of patients with wheezing attributable to BMI ≥ 85th percentile (8.2%) slightly exceeded those identified with abdominal obesity, WC ≥ 80th percentile (7.3%) and WHtR > 0.5 (7.1%)., Conclusion: The results suggest that an excess of fat deposits, either in the abdominal region or elsewhere in the body, increased the risk of wheezing. Since obesity is an important public health problem worldwide, control of this problem may partially reduce the occurrence of wheezing in youth.

Background: The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent., Objective: We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America., Methods: Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression., Results: Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (≥0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze., Conclusion: The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms., Competing Interests: of potential conflict of interest: R. L. Fiaccone receives research support from Brazilian National Research Council (CNPq). A. A. Cruz receives research support from the Wellcome Trust, the Brazilian National Research Council (CNPq), and Fundacao de Amparo a Pesquisa da Bahia, Brazil (FAPESB) and is on the Board of Directors for the Global Initiative for Asthma (GINA) and Allergic Rhinitis and its Impact on Asthma. P. J. Cooper receives research support from the Wellcome Trust. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Toxocara canis and T. cati are parasites of dogs and cats, respectively, that infect humans and cause human toxocariasis. Infection may cause asthma-like symptoms but is often asymptomatic and is associated with a marked eosinophilia. Previous epidemiological studies indicate that T. canis infection may be associated with the development of atopy and asthma., Objectives: To investigate possible associations between Toxocara spp. seropositivity and atopy and childhood wheezing in a population of children living in non-affluent areas of a large Latin American city., Methods: The study was conducted in the city of Salvador, Brazil. Data on wheezing symptoms were collected by questionnaire, and atopy was measured by the presence of aeroallergen-specific IgE (sIgE). Skin prick test (SPT), total IgE and peripheral eosinophilia were measured. Toxocara seropositivity was determined by the presence of anti-Toxocara IgG antibodies, and intestinal helminth infections were determined by stool microscopy., Findings: Children aged 4 to 11 years were studied, of whom 47% were seropositive for anti-Toxocara IgG; eosinophilia >4% occurred in 74.2% and >10% in 25.4%; 59.6% had elevated levels of total IgE; 36.8% had sIgE≥0.70 kU/L and 30.4% had SPT for at least one aeroallergen; 22.4% had current wheezing symptoms. Anti-Toxocara IgG was positively associated with elevated eosinophils counts, total IgE and the presence of specific IgE to aeroallergens but was inversely associated with skin prick test reactivity., Conclusion: The prevalence of Toxocara seropositivity was high in the studied population of children living in conditions of poverty in urban Brazil. Toxocara infection, although associated with total IgE, sIgE and eosinophilia, may prevent the development of skin hypersensitivity to aeroallergens, possibly through increased polyclonal IgE and the induction of a modified Th2 immune reaction.

Introduction: Larva migrans visceral is caused by Toxocara sp and has never been studied in Bahia. This work investigated the prevalence and risk factors for infection by Toxocara canis in individuals from Salvador, State of Bahia., Methods: Three hundred and thirty-eight individuals were investigated for the presence of serum IgG anti-T. canis., Results: IgG anti-T. canis was higher in individuals from lower social classes who had more contact with dogs and cats, indicating that these variables are factors risk for this infection., Conclusions: The prevalence of T. canis infection was high. The risk factors for this infection identified are in agreement with in the literature.

Objective: This study aimed to explore the association between asthma and atopy in a cohort of children living in a large urban center in Brazil. Atopy was defined by the presence of allergen-specific IgE in serum or by a positive skin prick test., Methods: In a sample of 1 445 Brazilian children, the association between the prevalence of asthma, skin prick test positivity, and allergen-specific IgE in serum was investigated., Results: The prevalence of asthma was 22.6%. The presence of serum allergen-specific IgE was frequent in asthmatics and nonasthmatics, and the prevalence of asthma increased only with levels of allergen-specific IgE > 3.5 kilounits/L. The proportion of asthma attributable to atopy was estimated to be 24.5% when atopy was defined by the presence of allergen-specific IgE. With a given level of specific IgE, no association between skin test reactivity and asthma was observed. Skin prick tests were less sensitive than specific IgE for detection of atopy., Conclusions: Most asthma cases in an urban underprivileged setting in Brazil were not attributable to atopy. This observation has important implications for understanding the risk factors for the asthma epidemic in Latin America.