PLA2R1 and HLA-DQA1 gene variations in idiopathic membranous
nephropathy in South China

ABSTRACT Introduction: Associations of variations in PLA2R1 and HLA-DQA1 genes with susceptibility to idiopathic membranous nephropathy (IMN) have been well documented. Association with spontaneous remission, however, is poorly defined in the Chinese Han population. Methods: A Chinese cohort of 117 IMN patients and 138 healthy controls were recruited between July 2009 and November 2019. Case-control studies for single-nucleotide polymorphisms (SNPs) within HLA-DQA1 (rs2187668) and PLA2R1 (rs35771982, rs4664308, rs3749117, rs3749119) genes were performed. The contributions of these polymorphisms to predict susceptibility, titre of autoantibodies against the M-type phospholipase A2 receptor (anti-PLA2R1), glomerular PLA2R1 expression, and spontaneous remission were analysed. Results: We found that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) were strongly associated with IMN susceptibility, while SNP (rs2187668) within HLA-DQA1 did not increase the risk of IMN. All SNPs in PLA2R1 and HLA-DQA1 were not statistically associated with anti-PLA2R1 titre, glomerular PLA2R1 expression and spontaneous remission after Bonferroni correction (P>0.0167). Clinical and pathological parameters such as lower levels of serum albumin, higher levels of anti-PLA2R1 and glomerular PLA2R1 expression were independent risk factors for non-spontaneous remission. Conclusion: This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN. Keywords: HLA-DQA1, idiopathic membranous nephropathy, PLA2R1, susceptibility, spontaneous remission

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Membranous Nephropathy in Pregnancy

American Journal of Nephrology ◽

10.1159/000505175 ◽

2020 ◽

Vol 51 (4) ◽

pp. 304-317 ◽

Cited By ~ 2

Author(s):

Zi-ning Liu ◽

Zhao Cui ◽

Ying-dong He ◽

Yi-miao Zhang ◽

Fang Wang ◽

...

Keyword(s):

Risk Factors ◽

Serum Albumin ◽

Membranous Nephropathy ◽

Fetal Loss ◽

Urinary Protein ◽

Fetal Outcomes ◽

Child Bearing ◽

Phospholipase A2 Receptor ◽

Birth Weight Percentile

Background: Primary membranous nephropathy (pMN) is less common in women of child-bearing age. The kidney risk factors to adverse maternal-fetal outcomes and the effects of pregnancy on pMN process need to be investigated. Methods: We retrospectively screened all the patients with biopsy-proven pMN from 2008 to 2018. Any cases of pregnancy that occurred at the time of pMN diagnosis or during follow-up were included in the study. Clinical and pathological data were collected from all patients at the time of kidney biopsy and their gestational results were recorded. Results: Of the 27 pregnancies with gestational time of 35.9 ± 4.5 weeks, 10 adverse maternal-fetal events occurred, including fetal loss (11%), preterm delivery (26%), and severe preeclampsia (15%). The kidney parameters were relatively stable with all preserved kidney function. Time-averaged urinary protein (p < 0.001) and serum albumin (p < 0.001), maximum urinary protein (p = 0.001) and minimum serum albumin (p = 0.01) before week 20, anti-phospholipase A2 receptor (PLA2R) positivity (p = 0.03), and no remission during pregnancy (p = 0.004) were risk factors to adverse maternal-fetal outcomes. Time-averaged urinary protein and serum albumin correlated with the birth weight percentile of neonates. Conclusions: Pregnancy in pMN patients showed risks to adverse maternal-fetal events. Heavy proteinuria, especially before week 20 of gestation, severe hypoalbuminemia, positive anti-PLA2R, and no remission were risk factors to worse outcomes.

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Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy

BioMed Research International ◽

10.1155/2020/1693710 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Qiu-hua Zhang ◽

Mian Wu ◽

Zhi-gang Hu ◽

Xiao-bin Liu ◽

Biao Huang ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Serum Albumin ◽

Membranous Nephropathy ◽

Serum Antibody ◽

Chinese Patients ◽

Idiopathic Membranous Nephropathy ◽

Phospholipase A2 Receptor ◽

Secondary Membranous Nephropathy ◽

Clinical Correlations

Background. M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods. A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results. The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P<0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P=0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P=0.015) and serum albumin (23.28 vs. 27.95 g/L, P=0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P=0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion. Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

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The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China

BMC Medical Genomics ◽

10.1186/s12920-021-00969-0 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Shulei Fan ◽

Qiuxia Wang ◽

Amanda Y. Wang ◽

Ping Zhang ◽

Xiang Zhong ◽

...

Keyword(s):

Membranous Nephropathy ◽

Clinical Manifestations ◽

Human Leukocyte ◽

Western China ◽

Renal Outcome ◽

Nucleotide Polymorphisms ◽

Renal Outcomes ◽

Phospholipase A2 Receptor ◽

Hla Dqa1

Abstract Background Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort. Methods Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. Results Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 μmol/L vs. 122.8 ± 126.6 μmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 μmol/L vs. 392.8 ± 118.1 μmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m2 vs. 77.1 ± 35.3 ml/min/1.73m2, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype. Conclusions Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.

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Phospholipase‐A2 receptor antibody, 24 hours proteinuria, and serum albumin as indicators of cyclophosphamide efficacy in idiopathic membranous nephropathy

Journal of Clinical Laboratory Analysis ◽

10.1002/jcla.23368 ◽

2020 ◽

Vol 34 (9) ◽

Author(s):

Chunying Xiao ◽

Yong Liu ◽

Xinpeng Zhang ◽

Lin Luo ◽

Xiaoying Li ◽

...

Keyword(s):

Serum Albumin ◽

Phospholipase A2 ◽

Membranous Nephropathy ◽

Idiopathic Membranous Nephropathy ◽

Receptor Antibody ◽

Phospholipase A2 Receptor

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The Association Between Variants in PLA2R and HLA-DQA1 and Renal Outcomes in Patients With Primary Membranous Nephropathy in Western China

10.21203/rs.3.rs-136132/v1 ◽

2020 ◽

Author(s):

Shulei Fan ◽

Qiuxia Wang ◽

Amanda Y Wang ◽

Ping Zhang ◽

Xiang Zhong ◽

...

Keyword(s):

Membranous Nephropathy ◽

Clinical Manifestations ◽

Human Leukocyte ◽

Western China ◽

Renal Outcome ◽

Nucleotide Polymorphisms ◽

Renal Outcomes ◽

Phospholipase A2 Receptor ◽

Hla Dqa1

Abstract Background：Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort.Methods: Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. Results: Eight SNPs were not associated clinical manifestations of PMN patients (Pc<0.05). rs3828323 T allele was marginally significantly associated with hypertension (P=0.008, Pc=0.064, OR=1.821). After treatment for PMN, urea (OR=1.184, 95%CI:1.030-1.361, P=0.017) was a risk factor for non-remission of the disease, eGFR (OR=0.984, 95%CI:0.970-0.998, P=0.028) and albumin (OR=0.922, 95%CI:0.880-0.966, P=0.001) were protective factors for non-remission of the disease. We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype.Conclusions：Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.

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