The common IL1A single nucleotide polymorphism rs17561 is a hypomorphic mutation that significantly reduces interleukin-1α release from human blood cells.

ABSTRACT: Interleukin-1 alpha (IL-1α) is a powerful cytokine that drives inflammation and modulates adaptive immunity. Due to these powerful effects, IL-1α is controlled at multiple levels from transcription to cleavage and release from the cell. Genome-wide association studies can identify loci that drive important diseases, although often the functional effect of the variant on phenotype remains unknown or small, with most risk variants in non-coding regions. We find that the common variant rs17561 changes a conserved amino acid in the central region of IL-1α linking the pro piece to the cytokine domain. Using a recall-by-genotype study and whole blood stimulation, we find that minor allele homozygotes release ~50% less IL-1α than the major allele, with IL-1β release equivalent. IL-1α transcript l

SUBMITTER: Wiggins KA 

PROVIDER: S-EPMC11495263 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature