In cultured airway epithelial cells, rs1420101 (blue) — but not rs11685480 (red) or rs1921622 (black) — is associated with sST2 gene expression (n = 127) (A) and sST2 secreted protein levels (n = 141) (B) in both the unstimulated and IL-13–stimulated conditions. White non-Hispanic subjects are indicated with a circle, while the entire cohort is indicated with a square. SNP regression coefficient and the corresponding 95% CIs are plotted. Additive linear regression models were used. *P < 0.05, **P < 0.01. (C) In contrast, both rs1420101 (blue) and rs11685480 (red) are associated with sST2 gene expression in distal lung parenchymal tissue in GTEx cadaveric donors (n = 237). SNP regression coefficient and the corresponding 95% CIs are plotted with P value listed below. Additive linear regression models were used. (D) Schema showing that sST2 transcripts can be derived from either the IL1RL1 distal or proximal promoters. sST2 transcripts derived from the distal promoter will contain exon 1a, while those derived from the proximal promoter will contain exon 1b. Primers were designed to specifically amplify exon 1a and exon 1b, as indicated by black arrowheads. (E) Cultured human airway epithelial cells (n = 6) and cultured human lung endothelial cells (n = 3) use the proximal promoter, while human alveolar epithelial cells (n = 7) use both promoters. *P < 0.05, ***P < 0.001 using 2-tailed paired t test.