rs2637988

This genome-wide association study (GWAS) identified genetic variants influencing interleukin levels in African Americans. IL-10 levels showed genome-wide significant associations with 8 SNPs, most notably rs5743185 in PMS1 (p=2.30×10⁻¹⁰), with successful replication of rs17365948 in YWHAZ. IL-1Ra levels showed suggestive associations with SNPs in ASB3 and the IL-1 gene family, with replication of rs4251961. IL-6 levels showed genome-wide significant association with one variant near RP11-314E23.1 (p=8.63×10⁻⁹).

Meta-analysis of five case-control studies (302 IPF patients, 879 controls) showing that the IL1RN VNTR*2 haploblock (combining VNTR with rs408392 and rs419598 minor alleles) is significantly associated with idiopathic pulmonary fibrosis risk (allelic model OR=1.42, p=0.002; dominant model OR=1.60, p=0.002). rs2637988 GG genotype was associated with lower IL1RN mRNA expression levels in healthy controls (p<0.001), suggesting the mechanism involves reduced IL-1Ra protein that fails to counteract pro-fibrotic IL-1.