Patterns of GATA3 and IL13 gene polymorphisms associated with childhood rhinitis and atopy in a birth cohort.

ABSTRACT

BACKGROUND: GATA3 activates transcription of the T(H)2 cytokines, including IL13, an important step in the allergic inflammatory pathway. OBJECTIVE: We sought to identify associations of single nucleotide polymorphisms of the genes GATA3 and IL13 and their interactions with rhinitis and allergic sensitization during childhood. METHODS: We performed genetic association studies in a cohort of children (n = 923) who have been evaluated for the development of rhinitis and allergic sensitization by means of skin prick tests (SPTs) at age 10 years. Pyrosequencing was used to genotype 7 polymorphisms from GATA3 and 5 from IL13. A novel model-selection procedure combining logistic regression models and classification was used to study the contributions of the polymorphisms and their interactions. RESULTS: Combinations of polymorphisms and their interactions increase the risk for rhinitis and allergic sensitization at age 10 years. A model with rs1058240, rs379568, and rs4143094 (GATA3) and rs1800925 (IL13) and their interactions was selected to predict rhinitis and positive SPT responses. rs1058240 was associated with rhinitis and allergic rhinitis (P < .05), and the gene-gene interaction rs1058240rs1800925 was associated with rhinitis (P = .043). The odds ratios for 4 genotype combinations were significant for rhinitis or SPTs (P < .044). CONCLUSION: Gene-gene interaction between GATA3 and IL13 polymorphisms can influence the risk of childhood rhinitis. Our study suggests that set associations of polymorphisms are important in studying genetic associations for complex phenotypes, such as rhinitis and atopy.