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Meta-Analysis
. 2022 Dec 5;23(23):15331.
doi: 10.3390/ijms232315331.

Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis

Maria Tziastoudi  1 , Theoharis C Theoharides  2   3   4   5 , Evdokia Nikolaou  1 , Maria Efthymiadi  1 , Theodoros Eleftheriadis  1 , Ioannis Stefanidis  1
Affiliations
Meta-Analysis

Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis

Maria Tziastoudi et al. Int J Mol Sci. .

Abstract

Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). A systematic review and meta-analysis of all available genetic association studies regarding the genes that are included in signaling pathways related to RF were performed. The evaluated studies were published in English and they were included in PubMed and the GWAS Catalog. After an extensive literature review and search of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, eight signaling pathways related to RF were selected and all available genetic association studies of these genes were meta-analyzed. ACE, AGT, EDN1, EPO, FLT4, GREM1, IL1B, IL6, IL10, IL12RB1, NOS3, TGFB1, IGF2/INS/TH cluster, and VEGFA were highlighted as the key genetic components driving the fibrosis process in DN. The present systematic review and meta-analysis indicate, as key players of fibrosis in DN, sixteen genes. However, the results should be interpreted with caution because the number of studies was relatively small.

Keywords: diabetic nephropathy; genes; meta-analysis; renal fibrosis; review.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Venn diagram showing the overlap between genes in pathways.
Figure 2
Figure 2
Flowchart of retrieved articles with specification of the reasons for exclusion.
Figure 3
Figure 3
Meta-analysis results of diseased controls versus cases based on genotype counts.
Figure 4
Figure 4
Meta-analysis results of healthy controls versus cases based on genotype counts.
Figure 5
Figure 5
Meta-analysis results of healthy controls versus diseased controls versus cases based on genotype counts.
Figure 6
Figure 6
Meta-analysis results of diseased controls versus cases and healthy controls versus cases based on allele counts.
See this image and copyright information in PMC

References

    1. Rich S.S. Genetics of diabetes and its complications. J. Am. Soc. Nephrol. 2006;17:353–360. doi: 10.1681/ASN.2005070770. - DOI - PubMed
    1. Cowie C.C., Port F.K., Wolfe R.A., Savage P.J., Moll P.P., Hawthorne V.M. Disparities in incidence of diabetic end-stage renal disease according to race and type of diabetes. N. Engl. J. Med. 1989;321:1074–1079. doi: 10.1056/NEJM198910193211603. - DOI - PubMed
    1. Seaquist E.R., Goetz F.C., Rich S., Barbosa J. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N. Engl. J. Med. 1989;320:1161–1165. doi: 10.1056/NEJM198905043201801. - DOI - PubMed
    1. Thomas M.C., Groop P.H., Tryggvason K. Towards understanding the inherited susceptibility for nephropathy in diabetes. Curr. Opin. Nephrol. Hypertens. 2012;21:195–202. doi: 10.1097/MNH.0b013e328350313e. - DOI - PubMed
    1. Rutledge J.C., Ng K.F., Aung H.H., Wilson D.W. Role of triglyceride-rich lipoproteins in diabetic nephropathy. Nat. Rev. Nephrol. 2010;6:361–370. doi: 10.1038/nrneph.2010.59. - DOI - PubMed