Dataset Information

Roles of arginase variants, atopy, and ozone in childhood asthma.

ABSTRACT:

Background

Arginases (encoded by ARG1 and ARG2 genes) might play an important role in asthma pathogenesis through effects on nitrosative stress. Arginase expression is upregulated in asthma and varies with T(H)2 cytokine levels and oxidative stress.

Objective

We aimed to examine whether variants in these genes are associated with asthma and whether atopy and exposures to smoking and air pollution influence the associations.

Methods

Among non-Hispanic and Hispanic white participants of the Children's Health Study (n = 2946), we characterized variation in each locus (including promoter region) with 6 tag single nucleotide polymorphisms for ARG1 and 10 for ARG2. Asthma was defined by parental report of physician-diagnosed asthma at study entry.

Results

Both ARG1 and ARG2 genetic loci were significantly associated with asthma (global locus level P = .02 and .04, respectively). Compared with the most common haplotype within each locus, 1 ARG1 haplotype was associated with reduced risk (odds ratio [OR] per haplotype copy, 0.55; 95% CI, 0.36-0.84), and 1 ARG2 haplotype was associated with increased risk (OR per haplotype copy, 1.35; 95% CI, 1.04-1.76) of asthma. The effect of the ARG1 haplotype that was significantly associated with asthma varied by the child's history of atopy and ambient ozone (P(interaction) = .04 and .02, respectively). Among atopic children living in high-ozone communities, those carrying the ARG1 haplotype had reduced asthma risk (OR per haplotype copy, 0.12; 95% CI, 0.04-0.43; P(heterogeneity) across atopy/ozone categories = .008).

Conclusions

ARG1 and ARG2 loci are associated with childhood asthma. The association between ARG1 variation and asthma might depend on atopy and ambient ozone levels.

SUBMITTER: Salam MT

PROVIDER: S-EPMC2913574 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

Roles of arginase variants, atopy, and ozone in childhood asthma.

Salam Muhammad T MT Islam Talat T Gauderman W James WJ Gilliland Frank D FD

The Journal of allergy and clinical immunology 20090301 3

<h4>Background</h4>Arginases (encoded by ARG1 and ARG2 genes) might play an important role in asthma pathogenesis through effects on nitrosative stress. Arginase expression is upregulated in asthma and varies with T(H)2 cytokine levels and oxidative stress.<h4>Objective</h4>We aimed to examine whether variants in these genes are associated with asthma and whether atopy and exposures to smoking and air pollution influence the associations.<h4>Methods</h4>Among non-Hispanic and Hispanic white part ...[more]

PMID: 19281908

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Project description:Study questionAre children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions?Summary answerInfertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy.What is known alreadyAsthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments.Study design, size, durationUpstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up.Participants/materials, setting, methodsWomen reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure.Main results and the role of chanceCompared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI).Limitations, reasons for cautionChildhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association.Wider implications of the findingsThough future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age.Study funding/competing interest(s)This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose.Trial registration numberN/A.

Dataset Information

Roles of arginase variants, atopy, and ozone in childhood asthma.

Background

Objective

Methods

Results

Conclusions

Publications

Roles of arginase variants, atopy, and ozone in childhood asthma.

Similar Datasets

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