Cytokine Polymorphisms and Relationship to Disease

Cytokines are polypeptide mediators produced by a variety of cell types that play crucial roles in immune and inflammatory responses. Genes that code for cytokines are highly polymorphic, and some of these polymorphisms directly or indirectly influence cytokine expression. The most frequent types of mutations are characterized by a change in a single nucleotide base pair and are called single nucleotide polymorphisms (SNPs). Many SNPs that affect cytokine expression represent disease modifiers and influence the severity or progression of immune-mediated and chronic inflammatory diseases. SNPs in cytokine genes have been associated with common diseases, including cardiovascular diseases, cancer, neurodegenerative diseases, allergy, and asthma, and data are now accumulating on their role in occupational/environmental diseases. All these diseases are multigenic and multifactorial in nature and involve interactions between genetic, physiological, and environmental factors. Currently, there exist inconsistencies in association studies examining relationships between cytokine SNPs and disease because of known limitations in population-based studies. Recent advances in geno typing platforms for largescale genetic studies, more robust study designs, and haplotype analysis should help reduce the amount of spurious and inconsistent associations in the literature and allow for incorporating genetic information into the risk assessment process although challenges still remain.