Genetic variants in 17q12-21 locus and childhood asthma in Brazil: Interaction with Varicella zoster virus seropositivity

Abstract

BackgroundAsthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. ObjectiveThis study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. MethodsThis was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). ResultsFour SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44–3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. ConclusionsWe confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.