Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Yoshikawa M

PROVIDER: S-EPMC7403323 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Yoshikawa Masahiro M Asaba Kensuke K

Scientific reports 20200804 1

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 4,39 ...[more]

PMID: 32753608

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Project description:BACKGROUND AND OBJECTIVES: Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ ?-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A Spanish cohort of 89 IMN patients and 286 matched controls without nephropathy was recruited between October of 2009 and July of 2012. Case-control studies for SNPs within HLA-DQA1 (rs2187668) and PLA2R1 (rs4664308) genes and CNVs for FCGR3A and FCGR3B genes were performed. The contribution of these polymorphisms to predict clinical outcome and renal function decline was analyzed. RESULTS: This study validated the association of these HLA-DQA1 and PLA2R1 SNPs with IMN in a Spanish cohort and its increased risk when combining both risk genotypes. No significant association was found between FCGR3 CNVs and IMN. These results revealed that HLA-DQA1 and PLA2R1 genotype combination adjusted for baseline proteinuria strongly predicted response to immunosuppressive therapy. HLA-DQA1 genotype adjusted for proteinuria was also linked with renal function decline. CONCLUSION: This study confirms that HLA-DQA1 and PLA2R1 genotypes are risk factors for IMN, whereas no association was identified for FCGR3 CNVs. This study provides, for the first time, evidence of the contribution of these HLA-DQA1 and PLA2R1 polymorphisms in predicting IMN response to immunosuppressors and disease progression. Future studies are needed to validate and identify prognostic markers.

Project description:BackgroundThe aim of this study was to investigate the correlation between the phospholipase A2 receptor (PLA2R) gene polymorphism and idiopathic membranous nephropathy (IMN) in Heilongjiang Chinese.MethodsThirty-five patients with IMN confirmed by renal biopsy attending the Heilongjiang Hospital of Traditional Chinese Medicine between June 2021 and December of 2021 were selected as the IMN group, and a group of 25 healthy participants from the Physical Examination Center of Heilongjiang Hospital of Traditional Chinese Medicine were enrolled as healthy controls. Polymerase chain reaction (PCR) was used to identify and genotype 8 single-nucleotide polymorphism (SNP) loci (rs16844715, rs2715918, rs2715928, rs35771982, rs3749119, rs3828323, rs4665143, and rs6757188) of PLA2R and to analyze the PLA2R gene polymorphisms that correlated with IMN. SPSS 26.0 statistical software was used for data analysis, and the chi-squared (χ2) goodness-of-fit test was used to determine whether each SNP genotype and allele in the PLA2R gene complied with the Hardy-Weinberg equilibrium. The qualitative data were analyzed via χ2 or Fisher exact probability method. Logistic regression was used to analyze risk factors, and the odds ratios (ORs) values and 95% confidence intervals (CIs) were calculated. α=0.05 was taken as the test level, and P<0.05 was considered statistically significant.ResultsStatistically significant differences were found in the genotype and allele frequencies of rs35771982 and rs3749119 between the IMN and control groups (P<0.05). Logistic regression analysis showed that the genotypes rs35771982 GG and rs3749119 CC were associated with IMN susceptibility. Statistically significant differences in uric acid level were found between the rs35771982 GG and CG + CC genotypes (P<0.05), while statistically significant differences in serum albumin were detected between rs3749119 CC and the CT + TT genotypes (P<0.05). Multivariate logistic regression analysis showed that gender, age, and triglyceride levels affected the occurrence of IMN (P<0.05).ConclusionsThe PLA2R gene polymorphisms rs35771982 and rs3749119 in Heilongjiang Chinese may be related to IMN susceptibility and correlated with clinical indicators of IMN. Gender, age, and triglyceride levels may influence the occurrence of IMN.

Project description:BackgroundIdiopathic membranous nephropathy (IMN) is a noninflammatory autoimmune glomerulonephropathy. Based on the risk stratification for disease progression, conservative nonimmunosuppressive and immunosuppressive therapy strategies have been recommended. However, there remains challenges. Therefore, novel approaches to treat IMN are needed. We evaluated the efficacy of Astragalus membranaceus (A membranaceus) combined with supportive care or immunosuppressive therapy in the treatment of moderate-high risk IMN.MethodsWe comprehensively searched PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Database for Chinese Technical Periodicals, Wanfang Knowledge Service Platform, and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials assessing the two therapy methods.ResultsThe meta-analysis included 50 studies involving 3423 participants. The effect of A membranaceus combined with supportive care or immunosuppressive therapy is better than that of supportive care or immunosuppressive therapy along in regulating for improving 24 hours urinary total protein (MD = -1.05, 95% CI [-1.21, -0.89], P = .000), serum albumin (MD = 3.75, 95% CI [3.01, 4.49], P = .000), serum creatinine (MD = -6.24, 95% CI [-9.85, -2.63], P = .0007), complete remission rate (RR = 1.63, 95% CI [1.46, 1.81], P = .000), partial remission rate (RR = 1.13, 95% CI [1.05, 1.20], P = .0004).ConclusionsAdjunctive use of A membranaceus preparations combined with supportive care or immunosuppressive therapy have a promising treatment for improving complete response rate, partial response rate, serum albumin, and reducing proteinuria, serum creatinine levels compared to immunosuppressive therapy in people with MN being at moderate-high risk for disease progression. Given the inherent limitations of the included studies, future well-designed randomized controlled trials are required to confirm and update the findings of this analysis.

Dataset Information

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

Publications

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

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