Abstract
The latest meta-analysis of genome-wide linkage studies (GWLS) identified nine cytogenetic locations suggestive of a linkage with diabetic nephropathy (DN) due to type 1 diabetes mellitus (T1DM) and seven locations due to type 2 diabetes mellitus (T2DM). In order to gain biological insight about the functional role of the genes located in these regions and to prioritize the most significant genetic loci for further research, we conducted a gene ontology analysis with an over representation test for the functional annotation of the protein coding genes. Protein analysis through evolutionary relationships (PANTHER) version 16.0 software and Cytoscape with the relevant plugins were used for the gene ontology analysis, and the overrepresentation test and STRING database were used for the construction of the protein network. The findings of the over-representation test highlight the contribution of immune related molecules like immunoglobulins, cytokines, and chemokines with regard to the most overrepresented protein classes, whereas the most enriched signaling pathways include the VEGF signaling pathway, the Cadherin pathway, the Wnt pathway, the angiogenesis pathway, the p38 MAPK pathway, and the EGF receptor signaling pathway. The common section of T1DM and T2DM results include the significant over representation of immune related molecules, and the Cadherin and Wnt signaling pathways that could constitute potential therapeutic targets for the treatment of DN, irrespective of the type of diabetes.
Highlights
The genetic background of diabetic nephropathy (DN) remains obscure, unquestionable [1,2,3]
In the seven cytogenetic locations that were revealed to be significant in the type 2 diabetes mellitus (T2DM) subgroup meta-analysis of genome wide linkage studies (GWLS)
gene ontology (GO) Analysis Results In type 1 diabetes mellitus (T1DM) and regarding the principal molecular functions of the genes, most of the and regarding the principal molecular functions of the function genes, most of the genes involved in the binding process, catalytic activity, molecular regulation, genes are involved in the binding process, catalytic activity, molecular function regulaand transporter and molecular transducer activity
Summary
The genetic background of diabetic nephropathy (DN) remains obscure, unquestionable [1,2,3]. Many loci have been implicated in the genetic architecture of DN through different methodological approaches [4,5,6]. Genetic linkage studies and genetic association studies are the two main approaches used in the genetic dissection of DN and other complex traits [7,8]. Three genome wide linkage studies (GWLS) were conducted in probands with DN due to T1DM [9,10,11]. A novel locus at cytogenetic location 22q11 was identified as significant of linkage with DN. This study confirms the importance of previously indicated DN loci on 3q21–q25 and 19q13 [9]. Österholm et al suggest that the locus on 3q harbors a susceptibility gene for DN [10]
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