Genetic variants of MCP-1 and CCR2 genes and IgA nephropathy risk

Gao, Jie; Liu, Xinghan; Wei, Linting; Niu, Dan; Wei, Jiali; Wang, Li; Ge, Heng; Wang, Meng; Yu, Qiaoling; Jin, Tianbo; Tian, Tian; Dai, Zhijun; Fu, Rongguo

doi:10.18632/oncotarget.12847

Cited by 14 publications

(14 citation statements)

References 36 publications

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“…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: 94%

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

Kidney Blood Press Res

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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.

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Section: Resultsmentioning

confidence: 94%

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

Kidney Blood Press Res

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“…The infiltration of these cells plays an important role in the progression of both anti-Thy1 nephritis 4,15,] and immunoglobulin A (IgA) nephritis. 16,17 On the basis of the glomerular gene expression profiles, immune cell infiltration initially triggers inflammation on day 1, which plays a crucial role in the development of anti-Thy1 nephritis. The inhibition of immune cell infiltration alleviated MC proliferation and ECM accumulation.…”

Section: Discussionmentioning

confidence: 99%

“…13 CCL2 drives mononuclear macrophage infiltration. 16,[23][24][25] However, upstream regulators (particularly transcription factors) of the CCL2 pathway remain unknown. In the present study, DBP was an upstream regulator of CCL2 expression.…”

Section: Discussionmentioning

confidence: 99%

The role of transcriptional factor D-site-binding protein in circadian CCL2 gene expression in anti-Thy1 nephritis

et al. 2018

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Mesangial proliferative glomerulonephritis (MsPGN) is an inflammatory disease, but both the nature of disease progression and its regulation remain unclear. In the present study, we monitored the course of anti-Thy1 nephritis from days 1 to 5 and established gene expression profiles at each time point using microarrays to explore the development of inflammation. According to the gene expression profiles, macrophage infiltration (triggered by CCL2 activation) was evident on day 1 and enhanced inflammation over the next few days. We screened for genes with expression levels similar to CCL2 and found that the upregulation of the circadian gene albumin D-site-binding protein (DBP) was involved in CCL2 activation in mesangial cells. More importantly, CCL2 expression showed oscillatory changes similar to DBP, and DBP induced peak CCL2 expression at 16:00 a clock on day 1 in the anti-Thy1 nephritis model. We knocked down DBP through transfection with a small interfering RNA (siRNA) and used RNA sequencing to identify the DBP-regulated TNF-α-CCL2 pathway. We performed chromatin immunoprecipitation sequencing (ChIP-Seq) and the dual luciferase assay to show that DBP bound to the TRIM55 promoter, regulating gene expression and in turn controlling the TNF-α-CCL2 pathway. In conclusion, DBP-regulated circadian CCL2 expression by the TRIM55-TNF pathway in injured mesangial cells at an early stage, which promoted macrophage recruitment and in turn triggered infiltration and inflammation in a model of anti-Thy1 nephritis.

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“…Among these factors, genetic factors play an import role in the development and progression of IgAN [10]. Our previous studies also found that Megsin [11], MCP-1/CCR2 [12] and TLR1 [13] gene polymorphisms were associated with IgAN susceptibility in a Chinese Han population. However, the rs699 variant in AGT gene and rs5186 polymorphism in ATR1 genes did not confer the risk with IgAN [14].…”

Section: Introductionmentioning

confidence: 98%

Association Between <b><i>IFN-γ</i></b> Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population

Gao¹,

Wei²,

Liu³

et al. 2017

Kidney Blood Press Res

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Background/Aims: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN), however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. Methods: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561) in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR) with 95% confidence intervals (CI). Results: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035). IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04). Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. Conclusions: IFN-γ polymorphisms may be involved in the development and progression of IgAN.

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Genetic variants of MCP-1 and CCR2 genes and IgA nephropathy risk

Cited by 14 publications

References 36 publications

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

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

The role of transcriptional factor D-site-binding protein in circadian CCL2 gene expression in anti-Thy1 nephritis

Association Between <b><i>IFN-γ</i></b> Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population

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