A prognostic signature based on genes associated with m6A/m5C/m1A/m7G modifications and its immunological characteristics in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by a high incidence and mortality rate. Despite advancements in therapeutic interventions, the prognosis for renal cancer patients remains suboptimal. Of late, methylation modifications have emerged as promising molecular targets for tumor assessment and treatment, yet their potential has not been fully investigated in the context of ccRCC. Transcriptomic and clinical data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress databases, leading to the identification of 57 methylation-related genes (MRGs). Utilizing DESeq2 analysis, Cox regression analysis, and the LASSO regression algorithm, a Methylation-Related Risk Score (MARS) was constructed. Cluster analysis, Gene Ontology (GO) analysis, clinical feature analysis, immune infiltration analysis, and mutation analysis were further employed to evaluate the model. Our investigation identified six pivotal prognostic MRGs and established a risk score predicated on m6A/m5C/m1A/m7G regulatory factors. This score was validated across two external cohorts and can be utilized to assess individual immune infiltration statuses and predict responses to immunotherapy. Moreover, cluster analysis delineated two distinct m6A/m5C/m1A/m7G gene clusters. We have developed and validated a robust prognostic signature based on genes associated with m6A, m5C, m1A, and m7G modifications. This gene signature demonstrates significant prognostic value in assessing survival outcomes, clinical characteristics, immune infiltration, and responses to immunotherapy in ccRCC patients. This finding provides valuable insights for refining precision treatment strategies.

Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

A novel technique for avoidance of sternotomy, diaphragmic incision and cardiopulmonary bypass during cavoatrial tumor thrombectomy for renal cell carcinoma with intraatrial tumor thrombus: a case series at a single center.

BACKGROUND: Radical nephrectomy with thrombectomy in patients with renal cell carcinoma (RCC) and level IV thrombus extending to the right atrium (RA) offers improved survival. However, this procedure is associated with significant perioperative morbidity and mortality. In this report, we describe a novel milking technique for patients with RA tumor thrombus using abdominal access, which does not require diaphragmic incision, sternotomy, right atriotomy, or cardiopulmonary bypass (CPB). METHODS: Between January 2019 and January 2022, four patients underwent resection of renal cell carcinoma extending into RA by a milking technique developed to avoid diaphragmic incision, sternotomy, or CPB. Patient characteristics, perioperative data, pathological features, and survival were evaluated. RESULTS: Complete resection was successful through pure transabdominal access without diaphragmic incision, sternotomy, or CPB in all patients. CONCLUSION: We conclude that radical nephrectomy and thrombectomy in optimized cases with renal cell carcinoma extending into RA can be safely and effectively performed without diaphragmic incision, sternotomy, or CPB, avoiding serious perioperative complications while providing acceptable oncological outcomes.

Protective effect of thymol on glycerol-induced acute kidney injury.

Acute kidney injury (AKI) is a syndrome characterized by an accelerating decrease in renal function in a short time. Thymol is one of the main components of thyme species and has a variety of pharmacological effects. Here, we investigated whether thymol could ameliorate rhabdomyolysis (RM)-induced AKI and its related mechanism. Glycerol was used to induce RM-associated AKI in rats. Rats received thymol (20 mg/kg/day or 40 mg/kg/day) gavage 24 h before glycerol injection until 72 h after injection daily. Kidney injury was identified by measuring serum creatinine (Scr) and urea levels and by H&E and PAS staining and immunohistochemistry (the expression of proliferating cell nuclear antigen (PCNA)). Renal superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress-related Nrf2/HO-1 signaling pathways were measured. The expression of the inflammatory markers TNF-α, IL-6, MCP-1, and NF-κB was assessed by ELISA and western blotting. Finally, the expression of the PI3K/Akt signaling pathway was detected by western blotting. Glycerol administration induced obvious renal histologic damage and increased Scr, urea, and PCNA expression. Notably, thymol treatment attenuated these structural and functional changes and prevented renal oxidative stress, inflammatory damage and PI3K/Akt pathway downregulation associated with glycerol-induced AKI. In conclusion, thymol might have potential applications in the amelioration of AKI via its antioxidant and anti-inflammatory effects and upregulation of the PI3K/Akt signaling pathway.

The feasibility and safety of adopting the left lumbar vein to localize the renal artery location during left transperitoneal laparoscopic partial nephrectomy.

Background: Laparoscopic partial nephrectomy (LPN) is the standard of care for localized small renal cancer. The most critical step in this form of surgery is to localize the renal artery. In the present study, we describe a novel technique that uses the left lumbar vein (LV) to access the left renal artery during LPN. Materials and methods: This was a retrospective review of 130 cases of transperitoneal laparoscopic partial nephrectomies (TLPNs) performed on patients with renal cancer in our center between January 2018 and December 2021. Either the LV or non-lumbar vein (N-LV) technique was used to locate and manage the left renal artery. We recorded relevant clinical data from all patients, including patient characteristics, tumor data, and perioperative outcomes (artery mobilization time, operative time, estimated blood loss, and complications). Comparative analysis was then carried out between the cases using LV or N-LV vein techniques. Results: All TLPNs were successfully accomplished without conversion to open approaches. There were no complications involving the renal vessels during the entire study. The LV technique resulted in a significantly shorter time to mobilize the renal and significantly less estimated blood loss (p < 0.05). There was no significant difference between the two techniques with regard to perioperative complications. Conclusion: The left LV represents an anatomical landmark for locating the left renal artery in TLPN. This approach has numerous advantages over the transperitoneal approach including facilitating access to the left renal artery and reducing the duration of surgery.

Pitfalls in the diagnosis and treatment of fat-poor angiomyolipoma of the renal pelvis mimicking urothelial carcinoma: report of three rare cases.

Angiomyolipoma (AML) represents the most frequent benign neoplasm of the kidney. It arises mostly in the cortex and protrudes into the perirenal space. It is extremely rare for a fat-poor AML to originate from the renal sinus, invade the pelvis, and present with hematuria. Because of the rarity of this lesion, differentiating it from a urothelial carcinoma is difficult, thereby making a preoperative diagnosis and management complex and challenging. We report three cases of fat-poor AML centered within the renal pelvis mimicking a urothelial carcinoma that underwent radical nephroureterectomy. The clinical characteristics, surgical management, and prognosis are discussed to achieve better preoperative evaluation of these entities. This is the first report of fat-poor AMLs involving the renal pelvis and presenting with hematuria. Nephron-sparing treatment is crucial for patients with these entities. Accurate diagnosis may allow partial resection or kidney-preserving treatment.

Surgical Management of a Giant Desmoid Fibromatosis of Abdominal Wall With Vessels Invasion in a Young Man: A Case Report and Review of the Literature.

Background: Desmoid fibromatosis (DF) is a rare clonal proliferation of fibroblasts and myofibroblasts. It develops in the connective tissues and does not metastasize but may infiltrate adjacent structures. Because of the rarity of these tumors and the unpredictable natural history of the disease, well-defined and precise guidelines of the optimal treatment for DF have not been formulated. Case Presentation: Here, we present a giant abdominal DF that invaded the right spermatic cord and iliac vessels. The lesion was excised with external iliac artery dissection; however, the vein was sacrificed. The abdominal wall defect was then repaired with a polypropylene mesh. The lesional cells are positive for ß-catenin. Conclusions: In the past decades, there has been a change in the treatment of DF. The "wait and see" policy has been considered initially in most cases. Surgical intervention remains a valid option for symptomatic lesions. The optimal regimes of the tumor should not take the risk of making the patient more symptomatic than the lesion itself.

Identification of New m6A Methylation Modification Patterns and Tumor Microenvironment Infiltration Landscape that Predict Clinical Outcomes for Papillary Renal Cell Carcinoma Patients.

N6-methyladenosine (m6A) is the product of the most prevalent mRNA modification in eukaryotic cells. Accumulating evidence shows that tumor microenvironment (TME) plays a pivotal role in tumor development. However, the underlying relationship between m6A modification and the TME of a papillary renal cell carcinoma (PRCC) is still unclear. To investigate the relationship between m6A modification and prognosis and immunotherapeutic efficacy for PRCC, we looked for distinct m6A modification patterns based on 23 m6A-related genes. Next, the correlation between m6A modification patterns and TME-related characteristics was investigated. Then, the intersected differentially expressed genes were selected and the scoring system, denoted as m6A score, was established to evaluate m6A modification, prognosis, and immunotherapeutic efficacy. In this study, three distinct m6A expression clusters were identified. Based on the results of immune cell infiltration analysis and functional analysis, carcinogenic pathways, TME-related immune cells, and pathways were identified as well. More importantly, the established m6A score showed good value in predicting clinical outcomes according to results using external cohorts. Specifically, PRCC patients with low m6A score value showed better survival, immunotherapeutic response, and higher tumor mutation burden. Furthermore, immunohistochemistry using PRCC clinical samples from our medical center was carried out and verified our results. In conclusion, this study highlights the underlying correlation between m6A modification and the immune landscape and, hence, enhances our understanding of the TME and improved the therapeutic outlook for PRCC patients.

Integrative Analysis of Immune-Related Genes in the Tumor Microenvironment of Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma.

Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

The Roles of CircRNAs in Bladder Cancer: Biomarkers, Tumorigenesis Drivers, and Therapeutic Targets.

Bladder cancer (BCa) is the most prevalent malignancy of the urinary system. Circular RNAs (circRNAs), a novel subtype of non-coding RNAs, play a crucial role in physiological and developmental processes. CircRNAs mainly function as regulators of splicing process and transcription, microRNA sponges, and protein brackets. Recent advances in understanding the pathogenesis of BCa have led to the identification of an abundance of dysregulated circRNAs associated with BCa. These aberrantly expressed circRNAs eventually lead to abnormalities in biological, genetic, and epigenetic information. In this review, we introduce the potential of circRNAs as biomarkers for BCa diagnosis and prognosis. Notably, diverse mechanisms have been proposed for circRNAs driving carcinogenesis, including increasing cell proliferation, promoting invasive and migratory capacity, enhancing endothelial-mesenchymal transition, sustaining stemness, and enabling resistance to chemotherapy. Importantly, a full understanding of circRNA mechanisms is needed to mine promising therapeutic approaches for targeting BCa. In this paper, we present the latest advances in circRNAs and systemically summarize the characteristics and mechanisms of circRNAs in BCa, providing potential perspectives for BCa treatment.

Comprehensive analysis of new prognostic signature based on ferroptosis-related genes in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor and the most common subtype of RCC. Ferroptosis is a novel form of regulated cell death, and ferroptosis-related genes (FRGs) have been associated with the prognosis of patients with certain cancers. However, the detailed prognostic correlation between FRGs and ccRCC has not yet been elucidated. To address this, the current study used The Cancer Genome Atlas (TCGA) dataset to explore 64 FRGs and determine their prognostic value in ccRCC. Results showed that 52 out of the 64 genes displayed significantly different expression levels in tumor tissue, and 35 out of the 52 differentially expressed genes (DEGs) were associated with overall survival. Subsequently, a four-gene prognostic signature (CD44, DPP4, NCOA4 and SLC7A11) was constructed and could successfully distinguish ccRCC patients with different prognosis in TCGA train and test sets. Furthermore, clinical ccRCC samples from our medical center were used to verify the application value of the new prognostic signature through immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Biological functional analysis implied that immune-related functions and pathways were enriched in the TCGA cohort and the immune status scores were significantly different between high- and low-risk sets. These results suggest that the four ferroptosis-related regulatory genes can act as reliable prognostic biomarkers of ccRCC, and might be exploited as potential targets of therapeutic strategies.

Comprehensive analysis of a new prognosis signature based on histone deacetylases in clear cell renal cell carcinoma.

Histone deacetylases (HDAC) family is vital for tumorigenesis and tumor progression. However, the exact role of the HDAC family in clear cell renal cell carcinoma (ccRCC) remains unclear. Based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and The Human Protein Atlas (HPA) database, we investigated and validated the expression profile, clinical significance and prognostic value of HDAC family members in ccRCC. Moreover, we further explored the correlation between HDACs and tumor microenvironment, tumor stemness, drug activity and immune subtype. The HDAC8, HDAC10, and HDAC11 manifested potential clinical value for prognosis, and the correlation analyses reveals underlying molecular mechanisms, which deserve further investigation for ccRCC. This Integrated bioinformatics analysis, based on transcriptomics and proteomics, implied that HDAC8, HDAC10, and HDAC11 may serve as potential molecular biomarkers and therapeutic targets for ccRCC, but some underlying molecular mechanisms still need to be elucidated.

NUPR1 is a novel potential biomarker and confers resistance to sorafenib in clear cell renal cell carcinoma by increasing stemness and targeting the PTEN/AKT/mTOR pathway.

BACKGROUND: Sorafenib can improve the survival of metastatic clear cell renal cell carcinoma (ccRCC) patients. However, its benefits are modest, as patients eventually become resistant, and the mechanisms remain elusive. NUPR1, a stress-induced protein, has been reported in malignancies and functions as an oncogene by modulating the stress response, facilitating survival in harsh environments and conferring drug resistance. However, its role in ccRCC has not been explored. METHODS: The expression and clinical significance of NUPR1 were analyzed in ccRCC patients in in-house patients and The Cancer Genome Atlas (TCGA) cohorts. The biological functions of NUPR1 were investigated. Xenografts were performed to confirm the effects of NUPR1 on tumorigenesis. The molecular mechanism of NUPR1 was investigated in vitro and in vivo. RESULTS: NUPR1 expression was upregulated in tumor tissue. Further analysis showed that NUPR1 overexpression was associated with an aggressive phenotype and predicted a poor prognosis. Depletion of NUPR1 suppressed tumorigenesis and sensitized cells to sorafenib treatment. Finally, mechanistic investigations indicated that NUPR1 promoted tumorigenesis in ccRCC by increasing stemness and activating the PTEN/AKT/mTOR signaling pathway. CONCLUSIONS: Collectively, our results suggest that NUPR1 may serve as a predictor of ccRCC. Notably, NUPR1 silencing reversed sorafenib resistance in ccRCC. These findings provide a novel potential therapeutic target in the clinical management of ccRCC.

Histone deacetylase 10, a potential epigenetic target for therapy.

Histone deacetylase (HDAC) 10, a class II family, has been implicated in various tumors and non-tumor diseases, which makes the discovery of biological functions and novel inhibitors a fundamental endeavor. In cancers, HDAC10 plays crucial roles in regulating various cellular processes through its epigenetic functions or targeting some decisive molecular or signaling pathways. It also has potential clinical utility for targeting tumors and non-tumor diseases, such as renal cell carcinoma, prostate cancer, immunoglobulin A nephropathy (IgAN), intracerebral hemorrhage, human immunodeficiency virus (HIV) infection and schizophrenia. To date, relatively few studies have investigated HDAC10-specific inhibitors. Therefore, it is important to study the biological functions of HDAC10 for the future development of specific HDAC10 inhibitors. In this review, we analyzed the biological functions, mechanisms and inhibitors of HDAC10, which makes HDAC10 an appealing therapeutic target.

Thymol alleviates lipopolysaccharide-stimulated inflammatory response via downregulation of RhoA-mediated NF-κB signalling pathway in human peritoneal mesothelial cells.

Thymol is one of the most important dietary constituents in the thyme species and has been shown to possess anti-inflammatory properties both in vivo and in vitro. We investigated the protective effects of thymol on the lipopolysaccharide (LPS)-induced inflammatory responses in the human peritoneal mesothelial cell line (HMrSV5) to clarify the potential mechanism. HMrSV5 cells were stimulated with LPS in the presence or absence of thymol. Our results showed that thymol markedly suppressed the production of cytokines such as tumour necrosis factor α (TNF-α), interleukin (IL)-6, monocyte chemoattractant protein 1 (MCP-1) and α-smooth muscle actin (α-SMA) in a dose-dependent manner. Western blot analysis indicated that RhoA and ROCK activation; Toll-like receptor 4 (TLR4) expression; and Nuclear factor -kappa B (NF-κB) p65, IKK and IκBα phosphorylation were also inhibited by thymol. Moreover, siRNA knockdown of RhoA suppressed the expression of pro-inflammatory cytokines and phosphorylation of NF-κB p65 and IκBα proteins in LPS-stimulated HMrSV5 cells, but did not affect TLR4 expression. In conclusion, thymol inhibits LPS-induced inflammation in HMrSV5 cells by suppressing TLR4-mediated RhoA-dependent NF-κB signalling pathway. Our study suggests that thymol may be a promising therapeutic agent against peritonitis.

Human neutrophil peptide 1-3, a component of the neutrophil extracellular trap, as a potential biomarker of lupus nephritis.

OBJECTIVE: Human neutrophil peptides (HNP) were recently implicated in the neutrophil extracellular trap (NET) complex, the impaired degradation of which has been associated with lupus nephritis (LN). METHODS: Forty LN patients, 40 SLE patients without kidney injury, 63 immunoglobulin A nephropathy (IgAN) patients, 20 minimal change disease (MCD) patients and 33 healthy controls were included in the present study. LN, IgAN and MCD patients were diagnosed with renal biopsy. LN patients were followed for a median period of 5.5 years. Clinical and laboratory data at the time of renal biopsy and follow-up were collected for each LN patient. Serum levels of HNP1-3 were measured with enzyme-linked immunosorbent assay. RESULTS: Serum HNP1-3 levels in LN patients were significantly higher than for SLE patients without kidney injury (P < 0.001), IgAN patients (P = 0.012), MCD patients (P = 0.010) and healthy controls (P = 0.022). Serum HNP1-3 levels were an independent indicator of LN (P = 0.006, OR = 7.5, 95% CI, 1.782-31.842), were statistically correlated with urinary protein excretion (P = 0.009) and activity index (P = 0.042) and were only marginally correlated with neutrophils (P = 0.054) and white blood cell counts (P = 0.051). Serum levels of HNP1-3 were a predictor of proteinuria remission after correction for multiple parameters (multivariate hazard 0.209; 95% CI 0.046-0.951; P = 0.043). CONCLUSIONS: The data from this study indicated that HNP1-3, one component of the NET, is a potential biomarker for LN.

Brief Report: identification of MTMR3 as a novel susceptibility gene for lupus nephritis in northern Han Chinese by shared-gene analysis with IgA nephropathy.

OBJECTIVE: Several novel susceptibility genes for systemic lupus erythematosus (SLE) and IgA nephropathy have been identified in recent genome-wide association studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases of the kidney, they may share common disease mechanisms that overlap with genetic susceptibility. To test this hypothesis, we sought to identify genetic variants associated with IgA nephropathy in lupus nephritis. METHODS: In the first stage, 500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500 healthy controls were enrolled. Fifteen single-nucleotide polymorphisms (SNPs) that had the topmost association signals with IgA nephropathy were selected for further testing in patients with lupus nephritis. Three independent cohorts from Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed the functional significance of identified noncoding variants on regulatory motifs and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: In addition to associations with HLA gene polymorphisms, genetic variants of MTMR3 in 22q12 showed associations with lupus nephritis (for rs9983A, OR 1.61 [95% CI 1.19-2.19], P = 2.07 × 10(-3) ) compared to healthy controls in the first stage. Associations were replicated and reinforced among northern Han Chinese (for lupus nephritis patients versus SLE patients without nephritis, P = 0.01) but not southern Han Chinese, although significant genetic heterogeneity was observed. Conservative and regulatory features of rs9983 were predicted in in silico analyses. In expression analysis, we observed lower MTMR3 transcription levels in samples of blood with rs9983A and in renal biopsy samples from lupus nephritis and IgA nephropathy patients. CONCLUSION: Our results suggest that the MTMR3 gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in SLE. However, widespread replication of these experiments, fine mapping, and functional assays are required to establish this connection.

A replication study from Chinese supports association between lupus-risk allele in TNFSF4 and renal disorder.

A recent phenotypic association study of genetic susceptibility loci in SLE suggested that TNFSF4 gene might be useful to predict renal disorder in lupus patients. To replicate the association, two single-nucleotide polymorphisms (SNPs: rs2205960 and rs10489265) were genotyped in 814 SLE patients. Correlations between genotypes and TNFSF4 expression were determined. The stainings of TNFSF4 in renal biopsy specimens were checked by immunohistochemistry. The SNPs of TNFSF4 were associated with renal involvement in lupus patients from the Chinese population (P values for rs2205960 and rs10489265 were 0.014 and 0.005 in additive model, resp.). An association between risk genotypes and low C3 levels was also observed (P = 0.034). Functional prediction suggested that rs2205960 had a regulatory feature. The risk alleles seemingly correlated with lower TNFSF4 expression. Strong TNFSF4 expression was detected in lymph nodes and "apparently normal" paratumor renal biopsy but not in renal biopsies from lupus nephritis. In genome-wide expression data, TNFSF4 was also observed to be downregulated in LN in both glomeruli and tubulointerstitium from kidney biopsies. However, the associations were marginally significant. Our data firstly replicated the association of TNFSF4 with renal disorder in SLE patients in the Chinese population, which supported that TNFSF4 may act as a marker of lupus nephritis. The detailed mechanisms of its role in pathogenesis will still be further needed.

FCGR2B and FCRLB gene polymorphisms associated with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a complex syndrome characterized by deposition of IgA and IgA containing immune complexes (ICs) composed of IgG and complement C3 proteins in the mesangial area of glomeruli. The low-affinity receptors for the Fc region of IgG (FcγRs) are involved in autoantibody/immune complex-induced organ injury as well as ICs clearance. The aim of the study was to associate multiple polymorphisms within FCGR gene locus with IgAN in a large Chinese cohort. PATIENTS AND METHODS: 60 single nucleotide polymorphisms (SNPs) spanning a 400 kb range within FCGR gene locus were analyzed in 2100 DNA samples from patients with biopsy proven IgAN and healthy age- and sex-matched controls from the same population in Chinese. RESULTS: Among the 60 SNPs investigated, 15 gene polymorphisms within FCGR gene locus (25%) were associated with susceptibility to IgAN. The most significantly associated SNPs within individual genes were FCGR2B rs12118043 (p = 8.74*10(-3), OR 0.76, 95% CI 0.62-0.93), and FCRLB rs4657093 (p = 2.28*10(-3), OR 0.77, 95% CI 0.65-0.91). Both conditional analysis and linkage disequilibrium analysis suggested they were independent signals associated with IgAN. Associations between FCGR2B rs12118043 and proteinuria (p = 3.65×10(-2)) as well as gross hematuria (p = 4.53×10(-2)), between FCRLB rs4657093 and levels of serum creatinine (p = 2.67×10(-2)) as well as eGFR (p = 5.41*10(-3)) were also observed. Electronic cis-expression quantative trait loci analysis supported their possible functional significance, with protective genotypes correlating lower gene expressions. CONCLUSION: Our data from genetic associations and expression associations revealed potentially pathogenic roles of Fc receptor gene polymorphisms in IgAN.