GENETIC POLYMORPHISMS RELATED TO INTERLEUKIN-1β PRODUCTION AND DISEASE RISK

Abstract

Purpose Interleukin (IL)-1A C-889T, IL-1B C-511T, IL-1B C-31T, IL-1B C3954T, and IL-1RN 86-bp VNTR (variable number of tandem repeats) are polymorphisms potentially influencing IL-1β production. This review summarizes 1) the biological roles of IL-1β, 2) allele frequencies of the polymorphisms, and 3) the reported associations between these polymorphisms and disease risk.
Methods Papers were obtained from PubMed with keywords “IL-1, polymorphism”, as well as from the references in each paper. The most relevant papers were then selected. In this review, a narrative approach was adopted.
Results IL-1β is a multifunctional proinflammatory cytokine, whose signal is transduced through IL-1 receptor I (IL-1RI) on the cell surface. Binding levels are influenced by the IL-1 receptor antagonist (IL-1Ra), IL-1RII (decoy receptor with no signal transduction), soluble IL-1RI, and soluble IL-1RII. IL-1B encoding IL-1β is located on chromosome 2q14, along with IL-1A encoding IL-1α and IL-1RN encoding IL-1Ra. The minor alleles, IL-1A -889T, IL-1B 3954T, and IL-1RN 2R, are rarer in Japanese than in Caucasians, while IL-1B -511T and IL-1B -31C are more frequent. These polymorphisms have been reported to have potential associations with the risk of diseases, such as stomach cancer, breast cancer, inflammatory bowel, Alzheimer's, and osteoporosis.
Discussion Although there are many inconsistent findings on associations with the polymorphisms, IL-1B C-511T and the tightly linked T-31C may be useful for predicting the risk of diseases with an inflammation basis among Japanese.