IL10 Family Member Genes IL19 and IL20 Are Associated With Recurrent Wheeze After Respiratory Syncytial Virus Bronchiolitis

Mechanisms underlying the increased risk of recurrent wheeze after respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are unclear. Specifically, information about genetic determinants of recurrent wheeze after RSV LRTI is limited. We performed a candidate gene association study to identify genetic determinants of recurrent wheeze after RSV LRTI. We investigated 346 single nucleotide polymorphisms (SNPs) in 220 candidate genes in 166 Dutch infants hospitalized for RSV LRTI. Logistic regression analysis was used to study associations between genotypes and haplotypes and recurrent wheeze after RSV LRTI. We found associations with recurrent wheeze for SNPs in IL19 , IL20 , MUC5AC , TNFRSF1B , C3 , CTLA4 , CXCL9 , IL4R , and IL7 genes. Haplotype analysis of the combined IL19/IL20 genotyped polymorphisms demonstrated an inverse association between the TGG haplotype and recurrent wheeze after RSV LRTI. IL19 and IL20 genes were notably associated with recurrent wheeze in infants without asthmatic parents. The association of IL20 SNP rs2981573 with recurrent wheeze was confirmed in a healthy birth cohort. We concluded that genetic variation in adaptive immunity genes and particularly in IL19/IL20 genes associates with the development of recurrent wheeze after RSV LRTI, suggesting a role for these IL10 family members in the etiology of airway disease during infancy.