Dataset Information

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

ABSTRACT:

Background

A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma.

Objectives

To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk.

Methods

We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped 4 single nucleotide polymorphisms (SNPs) of ARG1 and 4 SNPs of ARG2 with minor allele frequencies higher than 10% by using the TaqMan assay (Roche Molecular Systems, Pleasanton, Calif).

Results

ARG1 SNPs and haplotypes were not associated with asthma, but all 4 ARG1 SNPs were associated with the number of positive skin tests (P = .007-.018). Carrying 2 copies of minor alleles for either of 2 highly associated ARG2 SNPs was associated with a statistically significant increased relative risk (RR) of asthma (1.5, 95% CI = 1.1-2.1 for arg2s1; RR = 1.6, 95% CI = 1.1-2.3 for arg2s2). The association was slightly stronger among children with a smoking parent (arg2s1 RR = 2.1, 95% CI = 1.2 - 3.9 with a smoking parent; RR = 1.2, 95% CI = 0.8-1.9 without; interaction P = .025). Haplotype analyses reduced the sample size but supported the single SNP results. One ARG2 SNP was related to the number of positive skin tests (P = .027).

Conclusion

Variation in arginase genes may contribute to asthma and atopy in children.

SUBMITTER: Li H

PROVIDER: S-EPMC1450009 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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Publications

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

Li Huiling H Romieu Isabelle I Sienra-Monge Juan-Jose JJ Ramirez-Aguilar Matiana M Estela Del Rio-Navarro Blanca B Kistner Emily O EO Gjessing Håkon K HK Lara-Sanchez Irma Del Carmen Idel C Chiu Grace Y GY London Stephanie J SJ

The Journal of allergy and clinical immunology 20051128 1

<h4>Background</h4>A recent microarray study implicated arginase I (ARG1) and arginase II (ARG2) in mouse allergic asthma models and human asthma.<h4>Objectives</h4>To examine the association between genetic variation in ARG1 and ARG2 and childhood asthma and atopy risk.<h4>Methods</h4>We enrolled 433 case-parent triads, consisting of patients with asthma 4 to 17 years old and their biologic parents, from the allergy clinic of a public hospital in Mexico City between 1998 and 2003. Atopy to 24 a ...[more]

PMID: 16387594

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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

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

Background

Objectives

Methods

Results

Conclusion

Publications

Genetic polymorphisms in arginase I and II and childhood asthma and atopy.

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