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Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.

ABSTRACT: Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4-17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including two known functional SNPs [C-509T (rs1800469), T869C (rs1982073)] and three others (rs7258445, rs1800472, rs8179181), using TaqMan and Masscode assays. We analyzed the data using log-linear and polytomous logistic methods. Three associated SNPs, including the two known functional SNPs, were statistically significantly related to asthma risk. Individuals carrying the T allele of C-509T had an increased risk of asthma [relative risk (RR)=1.42, 95% confidence interval (CI)=1.08-1.87 for one copy; RR (95%CI)=1.95 (1.36-2.78) for two copies]. For T869C, the RRs (95%CI) were 1.47 (1.09-1.98) for one and 2.00 (1.38-2.90) for two copies of the C allele. Similar results were found for rs7258445. The haplotype containing all three risk alleles conferred an increased risk of asthma (RR=1.48, 95% CI=1.11-1.95 for one copy; RR=1.77, 95% CI=1.22-2.57 for two copies). These three SNPs were also related to the degree of atopy. This largest study to date of genetic variation in TGFB1 and asthma and atopy adds to increasing evidence for a role in these disorders.

SUBMITTER: Li H

PROVIDER: S-EPMC1865573 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.

Li Huiling H Romieu Isabelle I Wu Hao H Sienra-Monge Juan-Jose JJ Ramírez-Aguilar Matiana M del Río-Navarro Blanca Estela BE del Lara-Sánchez Irma Carmen IC Kistner Emily O EO Gjessing Håkon K HK London Stephanie J SJ

Human genetics 20070228 5

Transforming growth factor beta-1 (TGFB1) may influence asthma by modulating allergic airway inflammation and airway remodeling. The role of single nucleotide polymorphisms (SNPs) of TGFB1 in asthma remains inconclusive. We examined TGFB1 SNPs in relation to asthma risk and degree of atopy among 546 case-parent triads, consisting of asthmatics aged 4-17 years and their parents in Mexico City. Atopy to 24 aeroallergens was determined by skin prick tests. We genotyped five TGFB1 SNPs, including tw ...[more]

PMID: 17333284

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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 transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.

Publications

Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy.

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