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Meta-Analysis
. 2014 Oct 4:15:103.
doi: 10.1186/s12881-014-0103-8.

Meta-analysis of diabetic nephropathy associated genetic variants in inflammation and angiogenesis involved in different biochemical pathways

Nyla Nazir  1 , Khalid Siddiqui  2 , Sara Al-Qasim  3 , Dhekra Al-Naqeb  4
Affiliations
Meta-Analysis

Meta-analysis of diabetic nephropathy associated genetic variants in inflammation and angiogenesis involved in different biochemical pathways

Nyla Nazir et al. BMC Med Genet. .

Abstract

Background: Diabetes mellitus is the most common chronic endocrine disorder, affecting an estimated population of 382 million people worldwide. It is associated with microvascular and macrovascular complications, including diabetic nephropathy (DN); primary cause of end-stage renal disease. Different inflammatory and angiogenic molecules in various pathways are important modulators in the pathogenesis and progression of diabetic nephropathy. Differential disease risk in DN may be partly attributable to genetic susceptibility. In this meta-analysis, we aimed to determine which of the previously investigated genetic variants in these pathways are significantly associated with the development of DN and to examine the functional role of these genes.

Methods: A systematic search was conducted to collect and analyze all studies published till June 2013; that investigated the association between genetic variants involved in inflammatory cytokines and angiogenesis and diabetic nephropathy. Genetic variants associated with DN were selected and analyzed by using Comprehensive Meta Analysis software. Pathway analysis of the genes with variants showing significant positive association with DN was performed using Genomatix Genome Analyzer (Genomatix, Munich, Germany).

Results: After the inclusion and exclusion criteria for this analysis, 34 studies were included in this meta-analysis. 11 genetic variants showed significant positive association with DN in a random-effects meta-analysis. These included genetic variants within or near VEGFA, CCR5, CCL2, IL-1, MMP9, EPO, IL-8, ADIPOQ and IL-10. rs1800871 (T) genetic variant in IL-10 showed protective effect for DN. Most of these eleven genetic variants were involved in GPCR signaling and receptor binding pathways whereas four were involved in chronic kidney failure. rs833061 [OR 2.08 (95% CI 1.63-2.66)] in the VEGFA gene and rs3917887 [OR 2.04 (95% CI 1.64-2.54)] in the CCL2 gene showed the most significant association with the risk of diabetic nephropathy.

Conclusions: Our results indicate that 11 genetic variants within or near VEGFA, CCR5, CCL2, IL-1, MMP9, EPO, IL-8, ADIPOQ and IL-10 showed significant positive association with diabetic nephropathy. Gene Ontology or pathway analysis showed that these genes may contribute to the pathophysiology of DN. The functional relevance of the variants and their pathways can lead to increased biological insights and development of new therapeutic targets.

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Figures

Figure 1
Figure 1
Forest Plot for genetic variants involved in inflammatory cytokines and angiogenesis and significantly associated with diabetic nephropathy after meta-analysis.
Figure 2
Figure 2
Genetic variants significantly associated with diabetic nephropathy after meta-analysis in a subgroup; T1D- type 1 diabetes mellitus, T2D- type 2 diabetes mellitus, Cau-Caucasian origin, EDN- established diabetic nephropathy.
Figure 3
Figure 3
Genetic variants not significantly associated with diabetic nephropathy after meta-analysis in a subgroup; T1D- type 1 diabetes mellitus, T2D- type 2 diabetes mellitus, EDN- established diabetic nephropathy, ADN- advanced diabetic nephropathy.
Figure 4
Figure 4
Forest Plot for genetic variants involved in inflammatory cytokines and angiogenesis and not significantly associated with diabetic nephropathy after meta-analysis.
Figure 5
Figure 5
Genes involved in GPCR signaling Pathway: (G protein coupled-receptors are seven-transmemebrane receptors involved in signal transduction in humans).
Figure 6
Figure 6
Genes involved in receptor binding pathway.
Figure 7
Figure 7
Genes involved in chronic kidney failure (Disease Pathway).
See this image and copyright information in PMC

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References

    1. International Diabetes Federation: IDF Diabetes Atlas. 6th edition. Brussels, Belgium: International Diabetes Federation; 2013. [http://www.idf.org/diabetesatlas]
    1. Ezzidi I, Mtiraoui N, Kacem M, Mallat SG, Mohamed MB, Chaieb M, Mahjoub T, Almawi WY. Interleukin-10–592C/A, −819C/T and –1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients. Clin Endocrinol. 2009;70:401–407. doi: 10.1111/j.1365-2265.2008.03337.x. - DOI - PubMed
    1. Zhang D, Efendic S, Brismar K, Gu HF. Effects of MCF2L2, ADIPOQ and SOX2 genetic polymorphisms on the development of nephropathy in type 1 Diabetes Mellitus. BMC Med Genet. 2010;11:116. doi: 10.1186/1471-2350-11-116. - DOI - PMC - PubMed
    1. Freedman BI, Bostrom M, Daeihagh P, Bowden DW. Genetic Factors in Diabetic Nephropathy. Clin J Am Soc Nephrol. 2007;2:1306–131. doi: 10.2215/CJN.02560607. - DOI - PubMed
    1. Blech I, Katzenellenbogen M, Katzenellenbogen A, Wainstein J, Rubinstein A, Harman-Boehm I, Cohen J, Pollin TI, Glaser B. Predicting diabetic nephropathy using a multifactorial genetic model. PLoS One. 2011;6(4):e18743. doi: 10.1371/journal.pone.0018743. - DOI - PMC - PubMed

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