title: 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.
authors.affiliation: Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Li
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Juan-Jose
authors.initials: JJ
authors.lastname: Sienra-Monge
authors.forename: Matiana
authors.initials: M
authors.lastname: Ramírez-Aguilar
authors.forename: Blanca Estela
authors.initials: BE
authors.lastname: del Río-Navarro
authors.forename: Irma Carmen
authors.initials: IC
authors.lastname: del Lara-Sánchez
authors.forename: Emily O
authors.initials: EO
authors.lastname: Kistner
authors.forename: Håkon K
authors.initials: HK
authors.lastname: Gjessing
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008800:Mexico; D010290:Parents; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1