A systematic review and meta-analysis of genetic association studies for the role of inflammation and the immune system in diabetic nephropathy

Background: Despite the certain contribution of metabolic and haemodynamic factors in diabetic nephropathy (DN), many lines of evidence highlight the role of immunologic and inflammatory mechanisms. To elucidate the contribution of the immune system in the development of DN, we explored the contribution of gene variants (polymorphisms) in relevant pathophysiologic pathways. Methods: We selected six major pathways related to immune response from the Kyoto Encyclopaedia of Genes and Genomes database and thereafter we traced all available genetic association studies (GASs) involving gene variants in these pathways from PubMed and HuGE Navigator. Finally, we used meta-analytic methods for synthesizing the results of the GASs. Results: One hundred three GASs were retrieved that included 443 variants from 75 genes. Of those variants, 138 were meta-analysed and 61 produced significant results; seven variants were investigated in single GASs and showed significant association. Variants in CCL2, CCR5, IL6, IL8, EPO, IL1A, IL1B, IL100, IL1RN, GHRL, MMP9, TGFB1, VEGFA, MMP3, MMP12, IL12RB1, PRKCE, TNF and TNFRSF19 genes were associated with an increased risk of DN. Conclusions: There is evidence that variants related with immunologic response affect the course of DN. However, the present results should be interpreted with caution since the current number of available GASs is limited.