Cytokine polymorphisms and immunosenescence

Abstract

The influence of genetics on immunosenescence is still to be resolved. Common genetic variants (polymorphism) that reside within the genes encoding cytokines are candidates to positively or negatively affect immunosenescence. Cytokines regulate the type and magnitude of the immune function. Polymorphism can influence the expression level of the cytokine protein which can subsequently cause an imbalance in the cytokine cascade. Herein we examine the current literature with respect to cytokine polymorphisms in ageing and the age-related neurodegenerative disorder, Parkinson's disease. Ageing studies have identified two cytokine promoter polymorphisms that have shown repeated associations IL-6 (-174) and IL-10 (-1082). Others have failed to confirm these associations. This is due in part to studies of limited sample sizes examining a restricted number of cytokine polymorphisms. The inflammatory processes that characterize the cell death that is the hallmark of neurodegenerative disorders such as Parkinson's disease, may also be influenced by cytokine polymorphisms. However as with ageing, the results to date have been inconsistent although a number of studies have suggested the IL-1β?(-511) and TNF-α(-308) show significant association with Parkinson's disease susceptibility. Given the complexity of the cytokine network, and the dynamic interplay between anti and proinflammatory aspects, cross-sectional studies examining many cytokine variants in large sample series are now warranted. Genome-wide association studies may hold promise in resolving the role of cytokine polymorphisms in the inflammatory processes in both disease and ageing.