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The role of cytokines in diabetic nephropathy

We congratulate Wu et al for their comprehensive systematic review and metaanalysis to elucidate the contribution of polymorphisms of cytokine genes in the genetic susceptibility to diabetic nephropathy.1 The findings of the aforementioned study are supported by a systematic review and metaanalysis of genetic association studies about the role of inflammation and the immune system in diabetic nephropathy performed by our group.2 In our study, we focused on genes involved in six major pathways related to immune response as classified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and thereafter we traced all available genetic association studies (GASs) from PubMed, HuGE Navigator and the NHGRI Catalog of Published GenomeWide Association Studies (http://www.genome.gov/gwast udies/) concerning genes in the aforementioned KEGG pathways, and a few others with strong affinity regarding their function or relatedness to the other genes of the pathways. Finally, we used metaanalytic methods for synthesising the results of the GASs.2 The association between genotype distribution and diabetic nephropathy was examined using the generalised linear odds ratio (ORG). Our systematic review and metaanalysis involved 75 candidate genes from the six candidate pathways and 443 polymorphisms harboured in these genes out of which 138 variants were investigated in two or more studies and therefore their results were subject to metaanalysis. Significant associations based on metaanalysis results were reported for variants in CCL2, CCR5, IL6, IL8, EPO, IL1A, IL1B, IL10, IL1RN, GHRL, MMP9, TGFB1, VEGFA, MMP3, MMP12, IL12RB1, PRKCE, TNF and TNFRSF19 genes. These findings suggest that variants related to immunological response affect the course of diabetic nephropathy and are also consistent with other literature.3 The consistency about the contribution of IL1B, IL6, IL8, IL10 and TNF variants in the course of diabetic nephropathy which comes from both systematic reviews and metaanalyses provides conclusive evidence for the contribution of these genes that could merit prioritisation in the future studies of diabetic nephropathy genetics.