Gene polymorphism and risk of idiopathic membranous nephropathy

Li, Dongwei; Zhang, Jiahui; Shi, Yan; Liu, Zhangsuo

doi:10.1016/j.lfs.2019.05.010

Cited by 7 publications

(5 citation statements)

References 68 publications

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“…For example, lipopolysaccharide (LPS) derived from Escherichia coli ( E. coli ), which belongs to the phylum Proteobacteria , can induce the production of the cytokines tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) through the TLR4–NF-κB and TLR4–p38MAPK pathways, resulting in an inflammatory response ( Qiu et al, 2021 ). Polymorphisms in the Toll-like receptor 4 (TLR4) gene and the IL-6 gene were associated with IMN morbidity ( Liu et al, 2019 ). Moreover, genome-wide association studies (GWAS) in IMN patients revealed that a site on the NF-κB1 gene was associated with disease risk ( Xie et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Specific alterations of gut microbiota in patients with membranous nephropathy: A systematic review and meta-analysis

et al. 2022

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Background: The pathogenesis of idiopathic membranous nephropathy (IMN) has not yet been thoroughly clarified, and gut dysbiosis may be a contributor to IMN. However, the characterization of gut microbiota in patients with IMN remains uncertain.Methods: Cochrane Library, PubMed, China National Knowledge Internet, Web of Science, and Embase were used to search for studies through 18 May 2022. A meta-analysis based on the standardized mean difference (SMD) with 95% confidence interval (CI) was conducted on the alpha diversity index. The between-group comparison of the relative abundance of gut microbiota taxa and the beta diversity were extracted and qualitatively analyzed.Results: Five studies were included involving 290 patients with IMN, 100 healthy controls (HCs), and 129 patients with diabetic kidney disease (DKD). The quantitative combination of alpha diversity indices indicated that although bacterial richness was impaired [ACE, SMD = 0.12, (−0.28, 0.52), p = 0.55, I2 = 0%; Chao1, SMD = −0.34, (−0.62, −0.06), p < 0.05, I2 = 36%], overall diversity was preserved [Shannon, SMD = −0.16, (−0.64, 0.31), p = 0.50, I2 = 53%; Simpson, SMD = 0.27, (−0.08, 0.61), p = 0.13, I2 = 0%]. The beta diversity was significantly varied compared to HCs or DKD patients. Compared to HCs, the abundance of Proteobacteria increased, while that of Firmicutes decreased at the phylum level. Furthermore, the abundance of Lachnospira were depleted, while those of Streptococcus were enriched at the genus level. Proteobacteria and Streptococcus were also increased compared to DKD patients.Conclusions: The expansion of Proteobacteria and depletion of Lachnospira may be critical features of the altered gut microbiota in patients with IMN. This condition may play an important role in the pathogenesis of IMN and could provide bacterial targets for diagnosis and therapy.

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Section: Discussionmentioning

confidence: 99%

Specific alterations of gut microbiota in patients with membranous nephropathy: A systematic review and meta-analysis

et al. 2022

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“…Auto-Ab against thrombospondin type-1 domain-containing 7A (THSD7A) protein on podocyte membrane was identified in serum samples from anti-PLA2R1-negative IMN patients in 2014 35 . Although a study investigating the associations between SNPs in the THSD7A gene and IMN susceptibility has not yet been performed 6 , Zaghrini et al reported that the serum anti-THSD7A Ab titers appeared to be correlated with disease activity and with clinical outcome in a cohort with 49 MN patients who tested positive for anti-THSD7A Ab 36 . Moreover, several intracellular enzymes such as aldose reductase (AR), superoxide dismutase 2 (SOD2) and α-enolase were identified as target antigens in MN 37 .…”

Section: Discussionmentioning

confidence: 99%

“…Most cases of IMN undergo remission spontaneously or with immunosuppressive therapies. On the other hand, renal function gradually declines in refractory cases of IMN (about 30% of IMN cases), and renal replacement therapies may be necessary within a few decades of life 1 , 5 , 6 . Therefore, it is important to elucidate the pathology in more detail and to identify new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis

Yoshikawa

Asaba

2020

Sci Rep

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Although many studies investigated the associations between single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) gene and susceptibility to idiopathic membranous nephropathy (IMN), some showed inconsistent results. Here, we conducted a meta-analysis examining the associations between PLA2R1 SNPs and IMN susceptibility after systematic searches in the PubMed and Web of Science databases. Our meta-analysis for rs4664308 A>G including 2,542 IMN patients and 4,396 controls in seven studies showed a significant association between the G allele and a lower risk of IMN, as determined using an allelic model (odds ratio, 0.45; 95% confidence interval [0.41–0.50]), an additive model (for GG vs. AA: 0.26; [0.21–0.33]; for AG vs. AA: 0.40; [0.36–0.45]), a dominant model (0.37; [0.34–0.42]) and a recessive model (0.38; [0.31–0.48]). Our meta-analysis also suggested associations between rs3828323, rs35771982, rs3749117 and rs3749119 and IMN susceptibility although high heterogeneities and/or publication biases were observed. We did not study in our meta-analysis, but other studies indicated that high-risk genotype combinations of rs2187668 in the human leucocyte antigen-DQ a-chain 1 gene and rs4664308 in the PLA2R1 gene had even stronger associations and could affect the formation of anti-PLA2R1 antibodies, suggesting these SNPs could be novel therapeutic targets.

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“…Higher concentrations of PM2.5 are associated with a greater annual growth rate of MN. [1] The loss of immune tolerance leads to the formation of endogenous or exogenous antibodies in the body, forming immune complexes that can mediate kidney damage through the following pathways: (1) inducing podocytes to produce oxygen free radicals, (2) stimulating podocytes to produce various proteinases, causing GBM damage, (3) mediating the disruption and redistribution of essential membrane components, such as nephrin and podocin proteins, and affecting the microfilament skeletal structure in podocytes, (4) upregulating cyclooxygenase-2 (COX-2) in podocytes, leading to endoplasmic reticulum damage, (5) promoting the production of transforming growth factor beta (TGF-β) in podocytes to increase the extracellular matrix, leading to GBM thickening and glomerulosclerosis, (6) promoting podocyte apoptosis and detachment from the GBM, [9] (7) activating the complement system, leading to the formation of C5b-9 membrane attack complexes and directly damaging glomerular epithelial cells, causing proteinuria. [10] The generated C3a and C5a are potent chemotactic factors that attract leukocytes to the site of inflammation and exacerbate the kidney's inflammatory response.…”

Section: Etiology and Pathogenesis Of Mnmentioning

confidence: 99%

“…[3] Recent research has reported that single nucleotide polymorphisms, which are highly associated with the occurrence of IMN, exist at two gene loci. [4,5] These two loci are located at chromosome 2q24, encoding phospholipase A2 receptor gene (PLA2R), and at chromosome 6p21, encoding the human leukocyte antigen (HLA) complex class II molecule α chain 1A gene (HLA-DQA1). In addition, mutations in the THSD7A gene located on chromosome 7q33-q36.1 may also be associated with the occurrence of MN; [5] however, the exact cause remains unclear.…”

Section: Etiology and Pathogenesis Of Mnmentioning

confidence: 99%

Diagnosis and Treatment of Membranous Nephropathy in Integrative Medicine

Bi,

Guo,

et al. 2024

Integr Med Nephrol Androl

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Membranous nephropathy (MN) is a common glomerular disease. The related pathological changes are primarily characterized by the deposition of immune complexes beneath the epithelial cells of the glomerular basement membrane, accompanied by diffuse thickening of the basement membrane. Its etiology and pathogenesis are not fully understood yet; however, they are associated with genetics, infections, tumors, drugs, heavy metals poisoning, environmental pollution, and the loss of immune tolerance. Over 10 target antigens, including the phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A), associated with MN have been identified, each having different clinical implications. Clinical manifestations of MN patients mainly include proteinuria and nephrotic syndrome, with a propensity to form thrombi. Its diagnostic accuracy can be enhanced by combining clinical manifestations, serum antibody testing, and renal biopsy. Proteinuria, estimated glomerular filtration rate (eGFR), and PLA2R antibody levels are vital for the prognostic risk stratification of MN. Low-risk patients primarily undergo non-immunosuppressive treatment (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin II receptor blocker [ARB], sodium-glucose cotransporter 2 inhibitor [SGLT2i], anticoagulants, and traditional Chinese medicine [TCM] treatments), while high-risk patients need to consider using steroids and immunosuppressants, such as cyclophosphamide (CTX), calcineurin inhibitors (CNIs), and anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies. TCM holds that MN is the imbalance of Fei (lung), Pi (spleen), and Shen (kidney) function, leading to the generation of Neixie such as Shi, Re, Du, and Yu. This disease is difficult to heal because of Shire and Yu. The treatment is based on the use of Jianpi Bushen, simultaneously emphasizing the use of drugs for Qingre Qushi Huoxue. Dialectical use of TCM can obviously improve the clinical response rate and alleviate symptoms such as edema and fatigue by increasing the serum albumin level more rapidly while introducing fewer adverse reactions. Combined with Western medicine, TCM can also reduce toxicity and increase efficiency. This article systematically reviews the etiology, podocyte antigens, clinical manifestations, diagnostic approaches, risk assessment, and integrative medicine therapeutic strategies for MN, aiming to deepen the understanding of MN and guide clinical practice.

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Gene polymorphism and risk of idiopathic membranous nephropathy

Cited by 7 publications

References 68 publications

Specific alterations of gut microbiota in patients with membranous nephropathy: A systematic review and meta-analysis

Specific alterations of gut microbiota in patients with membranous nephropathy: A systematic review and meta-analysis

Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis

Diagnosis and Treatment of Membranous Nephropathy in Integrative Medicine

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