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Meta-analysis of diabetic nephropathy associated genetic variants in inflammation
and angiogenesis involved in different biochemical pathways
#MMPMID25280384
Nazir N
; Siddiqui K
; Al-Qasim S
; Al-Naqeb D
BMC Med Genet
2014[Oct]; 15
(?): 103
PMID25280384
show ga
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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