Impact of inflammatory cytokine and adipokine gene variations in the development of HIV‐associated lipodystrophy

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro‐inflammatory cytokines IL‐1, TNF‐α and IL‐6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro‐inflammatory cytokines (IL‐1, IL‐6 and TNF‐α). Plasma levels of cytokines such as TNF‐α, IL‐6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV‐associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD. The association of inflammatory cytokine gene IL‐1β − 511C/T and +3954C/T, IL‐1RN(VNTR) and TNF‐α − 308G/A polymorphisms with HIVLD have not been reported. Polymorphisms (IL‐6 − 174G/C and −572G/C, IL‐8 − 251A/T and +781C/T, IL‐10 − 592C/A, IL18 − 607C/A and −137C/G) have not been analyzed in HIVLD. Adipokine gene polymorphisms (APM1 − 11377G/C, ADIPOQ + 45 T/G, ADIPOQ + 276G/T, LEP − 2548 G/A, rest − 420G/C) and susceptilbity to HIVLD have not been reported previously. The role of TNF‐α (rs361525) and APM1 (rs266729) polymorphisms in HIVLD have been demonstrated. These candidate genes will be explored to define a pharmacogenomic strategy to identify patients at high risk of metabolic disorders upon antiretroviral therapy.