PDGF-B gene single-nucleotide polymorphisms are not predictive for disease onset or progression of IgA nephropathy

Abstract

Background: Few genetic factors have been identified that determine susceptibility to and progression of IgA-nephropathy (IgAN). Given that IgAN is usually characterized by mesangioproliferative glomerulonephritis and that PDGF-B is of central pathophysiological relevance in this process, we analyzed four single-nucleotide polymorphisms (SNPs) of the PDGF-B gene to evaluate a possible association of these SNPs with disease onset and progression, histological grading and responses to ACE inhibitor (ACEi) therapy. Methods: The total study population consisted of 195 IgAN patients (127 from southern Italy and 68 from northern Germany) and 200 healthy controls (100 from each region). All four SNPs were in Hardy-Weinberg equilibrium and genotype distributions did not differ between patients and controls in either region. Results: SNP distribution in Italian patients reaching endstage renal disease (n = 45) also was not significantly different from patients maintaining a serum creatinine below 1.2 mg/dl (n = 60) during 5.6 ± 5.5 years of follow-up. Furthermore, we failed to detect significant effects of any SNP on the slope of 1/serum creatinine, proteinuria level or the antiproteinuric response to ACEi. Additionally, particular PDGF-B genotypes did not correlate with histological grading using the Lee classification. Conclusion: We conclude that none of the four PDGF-B SNPs is related to the onset of IgAN in two different populations and that none of them has a major influence on the course of IgAN.

The Relationships between Polymorphisms in Genes Encoding the Growth Factors TGF-β1, PDGFB, EGF, bFGF and VEGF-A and the Restenosis Process in Patients with Stable Coronary Artery Disease Treated with Bare Metal Stent

“…This polymorphism has been associated with a risk of scleroderma development [ 17 ]. No relationship was observed between the risk of type 1 diabetes and IgA nephropathy development and the rs2285094 genotype [ 15 , 16 ]. In our analysis, we observed higher LLL in the C/C homozygote group, even after correction for angiographic variables, suggesting that this result is not an artefact.…”

“…The association of the rs2285094 polymorphism of the PDGFB gene, which is located in an intron near an mRNA splice site, with the development of type 1 diabetes [ 15 ], IgA nephropathy [ 16 ], and scleroderma [ 17 ] has been analysed. The rs308395 polymorphism within the bFGF gene promoter may influence transcription factors binding, and thus bFGF expression [ 18 , 19 ].…”

Correlation between platelet‐derived growth factor‐B gene polymorphism and coronary heart disease

“…While all these were not related to SNP rs1800818. Bicanski et al 29 investigated IgA nephropathy patients in Germany and Italy and found that four SNP polymorphism sites of PDGF‐B gene (rs2285094, rs2040399, rs2267406, rs2285097), allele distributions matched the Hardy–Weingerg linkage equilibrium, and each SNP genotype distribution was not related to disease onset and severity. Anat et al 30 studied 70 patients with heart transplantation and found that patients with GG genotype at PDGF‐B gene SNP rs1800818 had lower cardiac allograft vasculopathy (CAV) rate, longer survival time, and lower fatality rate.…”

“…While all these were not related to SNP rs1800818. Bicanski et al29 investigated IgA nephropathy patients in Germany and Italy and found that four SNP polymorphism sites of…”

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease

“…There was, however, one study associating rs2285094, which is located near the splice site, with higher incidence of sclerodermia [34]. This polymorphism was also tested for possible associations with type 1 diabetes [35] and IgA nephropathy [36], though no relationship was found. We also did not detect any association between rs2285094 and CAD burden.…”