Association Between &lt;b&gt;&lt;i&gt;IFN-γ&lt;/i&gt;&lt;/b&gt; Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population

Background/Aims: Arterial fibrotic intimal thickening and arteriolar hyaline are considered common pathological features in immunoglobulin A nephropathy (IgAN), whereas little is known about the acute pathological manifestations of endothelial cell injury. The aim of this study was to investigate characteristics of intrarenal arterial lesions and to estimate their prognostic values in patients with IgAN. The primary renal endpoint was a 50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). Methods: Various renal arterial lesions (arterial fibrotic intimal thickening, arteriolar hyaline, arteriolar endotheliocyte swelling, arteriolar inflammatory cell infiltration, and arteriolar thrombosis) in 1683 patients with IgAN were reviewed and reclassified using a semi-quantitative scoring system. Their correlations with clinical features, pathological characteristics, and renal outcomes were evaluated. Results: The prevalence of intrarenal arterial lesions was up to 72.2% in IgAN patients. There were 978 patients (58.1%) with arterial fibrotic intimal thickening, 350 patients (20.8%) with arteriolar hyaline, 432 patients (25.7%) with arteriolar endotheliocyte swelling, 356 patients (21.2%) with arteriolar inflammatory cell infiltration and 43 patients (2.6%) with arteriolar thrombosis. Arterial fibrotic intimal thickening and arteriolar hyaline were strongly associated with higher mean arterial pressure (MAP) and reduced eGFR (P < 0.001) but were not related to proteinuria at the time of renal biopsy. In contrast, arteriolar endotheliocyte swelling and arteriolar thrombosis were correlated with heavier proteinuria as well as higher MAP and reduced eGFR. During follow-up, patients with vascular lesions received more renin-angiotensin system (RAS) blockade and less glucocorticoid and showed poorer renal outcomes. Univariate Cox model showed that the presence of renal vascular lesions [hazard ratio (HR) = 25.01, 95% confidence interval (CI): 6.19 to 101.03, P < 0.001] was a risk factor for renal outcomes. However, in multivariable Cox analysis, which included clinical factors and the Oxford-MEST-C, vascular lesions were not significantly associated with an increased risk of renal failure. Remarkably, the impact of vascular lesions on the survival from ESRD or 50% reduction in renal function was eliminated by the use of RAS blockade after adjustment for eGFR, proteinuria, and MAP. Conclusion: Our study demonstrates the high prevalence of vascular lesions, including the chronic and acute arterial pathological changes, in patients with IgAN. The presence of vascular lesions is associated with higher MAP, reduced eGFR and poorer renal outcomes, which could be influenced by the RAS blockade treatment.

Section: Discussionmentioning

confidence: 99%

Intrarenal Arterial Lesions Are Associated with Higher Blood Pressure, Reduced Renal Function and Poorer Renal Outcomes in Patients with IgA Nephropathy

Zhang

Sun

Zhou

et al. 2018

“…However, the exact pathogenesis remains unknown. Genome-wide association studies have reported that multiple gene polymorphisms are correlated with the susceptibility to IgAN [4-9], including HLA-DQB1/DRB1, CFHR1, CFHR3, and HORMAD2 gene variants; our former studies also showed that IL-10 [10] and IFN-γ [11] polymorphisms were associated with the development of IgAN. These findings indicate that genetic factors are associated with the development and progression of IgAN.…”

Section: Introductionmentioning

confidence: 68%

Rs1520220 and Rs2195239 Polymorphisms of IGF-1 Gene Associated with Histopathological Grades in IgA Nephropathy in Northwestern Chinese Han Population

Wei

Liu

et al. 2018

Self Cite

Background/Aims: Insulin-like growth factor-1 (IGF-1) plays important roles in cellular proliferation, differentiation, and growth. Previous studies showed that single-nucleotide polymorphisms (SNPs) of IGF-1 are associated with various diseases. This case-control study aimed to examine the relationship between IGF-1 polymorphisms and IgA nephropathy (IgAN) risk in a Chinese Han population. Methods: We recruited 351 IgAN patients and 310 healthy controls from Northwestern China. Sequenom MassARRAY was utilized to examine the genotypes of two common IGF-1 SNPs (rs1520220 and rs2195239). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between IGF-1 and IgAN. Results: Our study demonstrated that IGF-1 gene rs1520220 and rs2195239 polymorphisms did not confer susceptibility to IgAN. We found no correlation between gender, blood pressure, proteinuria, eGFR, and IgAN in both SNPs. However, the rs1520220 and rs2195239 variants were correlated with M1 and E1 in patients with IgAN (M0/M1: CC vs. CG+GG: OR = 1.62, P = 0.04; E0/E1: CC vs. CG+GG: OR = 1.95, P = 0.004; GG vs. GC+CC: OR = 1.90, P = 0.004, respectively). Conclusion: These results indicate that IGF-1 gene polymorphisms play crucial roles in the histopathological progression of IgAN in the Chinese Han population.

“…The study included 351 patients with IgAN (229 males and 122 females, mean age of 32 ± 11.9 years) and 310 age- and sex-matched healthy controls (186 males and 124 females, mean age of 35 ± 12.6 years), details as shown in our previous studies [19-21]. There were no statistically significant differences between the two groups in terms of age and sex ( P ﹥0.05).…”

Section: Resultsmentioning

confidence: 93%

The Endothelial Nitric Oxide Synthase Gene Polymorphism is Associated with the Susceptibility to Immunoglobulin a Nephropathy in Chinese Population

Gao

Wang

Wei

et al. 2017

Self Cite

Background/Aims: Endothelial nitric oxide synthase (eNOS) is one of the most important enzymes for producting nitric oxide (NO), which regulate the function of many organs and cells. The single nucleotide polymorphisms (SNPs) of eNOS were found to be associated with many kidney diseases. However, it is lack of relevant studies to evaluate the associations between eNOS polymorphisms and immunoglobulin A nephropathy (IgAN). This case-control study aimed to evaluate the relationship between eNOS polymorphisms and IgAN. Methods: We recruited 351 IgAN patients and 310 age- and sex-matched healthy controls from Northwest China. Sequenom MassARRAY was used to detect the genotypes of two common eNOS SNPs (rs1799983 and rs2070744). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by the Chi square test to evaluate the associations between eNOS and IgAN. Phase 2.1 was used to conduct haplotype analysis. Results: In the overall analysis, we found that the rs1799983 polymorphism was associated with a decreased risk of IgAN (G/T vs. G/G: OR=0.57, 95%CI=0.34–0.96; G/T+T/T vs. G/G: OR=0.52, 95%CI=0.31–0.86; G/T vs. G/G-T/T: OR=0.60, 95%CI=0.36–0.99; Log-additive model: OR=0.48, 95%CI=0.30–0.78). Haplotype analysis indicated that T_rs1799983C_rs2070744 is a protective factor against IgAN (OR=0.62, 95%CI=0.42––0.92). However, no significant differences were found between the two SNPs (rs1799983 and rs2070744) and clinical features (age, sex, blood pressure, and Lee’s grade) of IgAN. Conclusion: The eNOS gene rs1799983 polymorphism and T_rs1799983C_rs2070744 haplotype may reduce the risk of IgAN in Chinese populations.