Why is Chromosome 17q21 linked to Asthma?

Asthma is an inflammatory disorder of the airways associated with increased airway responsiveness and airway remodeling. Several genome wide association studies (GWAS) and non-GWAS studies have demonstrated a strong genetic linkage of chromosome 17q21 genes with asthma in populations of diverse ethnic backgrounds. In particular, SNPs in the 17q21 region are found within a large linkage disequilibrium (LD) block that contains not only the orosomucoid like-3 (ORMDL3) gene, but also includes other 17q21 genes i.e. gasdermin B (GSDMB), IKAROS family zinc finger 3 (IKZF3), and zona pellucida binding protein 2 (ZPBP2). Studies of mice expressing increased levels of the human ORMDL3 gene have demonstrated that these mice have spontaneous increased airway remodeling and airway responsiveness in the absence of airway inflammation. Further functional studies are needed to investigate whether some or all of these four genes could contribute to the pathogenesis of asthma.