Dataset Information

Association between PLA2R1 rs4664308 and susceptibility to idiopathic membranous nephropathy: Protocol for a systematic review and meta-analysis of case-control studies.

ABSTRACT: Previous studies have evaluated the association between the phospholipase A2 m-type receptor (PLA2R1) rs4664308 polymorphism and the risk of idiopathic membranous nephropathy (IMN), but the results need to be integrated. We hypothesized that the PLA2R1 rs4664308 polymorphism is associated with IMN risk in different ethnicities and assessed this hypothesis by using meta-analysis and case-control studies.A literature searches on PLA2R1 rs4664308 and IMN risk was conducted using the EMBASE, PubMed, Cochrane Library, and Chinese Medical Databases. The relationship between PLA2R1 rs4664308 and IMN risk was evaluated in 5 genetic models, namely, allelic (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) models. Subgroup analysis was conducted by ethnicity on Asian and non-Asian populations.Eight sets of data from 6 articles met study objectives were selected and 6797 subjects (IMN: 2324 Controls: 4,473) were included. Heterogeneity was found in the DG, HMG, and HTG models but not in the AG or RG models. The minor allele(G) of PLA2R1 rs4664308 showed a significant negative correlation with IMN risk in all genetic random models: odds ratio of AG: 0.44(0.37-0.51), RG: 0.35(0.29-0.42), DG: 0.38(0.31-0.48), HMG: 0.26(0.19-0.37), and HTG: 0.61(0.48-0.77; P?

SUBMITTER: Qiu JY

PROVIDER: S-EPMC7647530 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Association between PLA2R1 rs4664308 and susceptibility to idiopathic membranous nephropathy: Protocol for a systematic review and meta-analysis of case-control studies.

Qiu Jing Yi JY Wu Xuan Gao XG Zhang Ting T Park Sunmin S

Medicine 20201101 45

Previous studies have evaluated the association between the phospholipase A2 m-type receptor (PLA2R1) rs4664308 polymorphism and the risk of idiopathic membranous nephropathy (IMN), but the results need to be integrated. We hypothesized that the PLA2R1 rs4664308 polymorphism is associated with IMN risk in different ethnicities and assessed this hypothesis by using meta-analysis and case-control studies.A literature searches on PLA2R1 rs4664308 and IMN risk was conducted using the EMBASE, PubMed, ...[more]

PMID: 33157933

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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:Background and objectivesDifferent rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy.Design, setting, participants, & measurementsTwenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m2 at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses.ResultsRemissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (P=0.02) at month 6, respectively, and in 24 (86%) versus 18 (67%) participants (P=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3-9] and 9 [IQR, 6-12] months for NICE and GEMRITUX cohorts respectively (P=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0-10.8] versus 0.0 [IQR, 0.0-0.0] P<0.001 and 0.0 [IQR, 0.0-2.0] versus 16.5 [IQR, 2.5-31.0] P<0.001) at month 3, lower level of anti-PLA2R1 antibodies at month 6 (0.0 [IQR, 0.0-8.0] versus 8.3 [IQR, 0.0-73.5] P=0.03). In the combined study population, lower epitope spreading at diagnosis and higher rituximab levels at month 3 were associated with remissions at month 6 (13/26 (50%) versus 22/29 (76%) P=0.05 and 2.2 µg/ml [IQR, 0.0-10.9] versus 0.0 µg/ml [IQR, 0.0-0.0] P<0.001 respectively). All non-spreaders entered into remission whatever the protocol. Eight of the 41 participants who reached remission had relapses. Epitope spreading at diagnosis (8/8 (100%) versus 16/33 (48%) P=0.01) and incomplete depletion of anti-PLA2R1 antibodies at month 6 (4/8 (50%) versus 5/33 (9%) P=0.05) were associated with relapses.ConclusionsOur work suggests that higher dose rituximab protocol is more effective on depletion of B-cells and lack of epitope spreading is associated with remission of membranous nephropathy.

Dataset Information

Association between PLA2R1 rs4664308 and susceptibility to idiopathic membranous nephropathy: Protocol for a systematic review and meta-analysis of case-control studies.

Publications

Association between PLA2R1 rs4664308 and susceptibility to idiopathic membranous nephropathy: Protocol for a systematic review and meta-analysis of case-control studies.

Similar Datasets

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