Chromosome 17q12-q21 is the most replicated genetic locus for childhood-onset asthma. Polymorphisms in this locus containing ∼10 genes interact with a variety of environmental exposures in the home and outdoors to modify asthma risk. However, the functional basis for these associations and their linkages to the environment have remained enigmatic. Within this extended region, regulation of GSDMB (gasdermin B) expression in airway epithelial cells has emerged as the primary mechanism underlying the 17q12-q21 genome-wide association study signal. Asthma-associated SNPs influence the abundance of GSDMB transcripts as well as the functional properties of GSDMB protein in airway epithelial cells. GSDMB is a member of the gasdermin family of proteins, which regulate pyroptosis and inflammatory responses to microbial infections. The aims of this review are to synthesize recent studies on the relationship of 17q12-q21 SNPs to childhood asthma and the evidence pointing to GSDMB gene expression or protein function as the underlying mechanism and to explore the potential functions of GSDMB that may influence the risk of developing asthma during childhood.
Keywords: 17q12-q21; GSDMB; asthma; gene-by-environment interaction; pyroptosis.