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      HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy

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          Abstract

          Idiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN. After adjusting for HLA-DRB1*15:01 and HLA-DRB3*02:02, no other alleles showed significant association with PLA2R-related MN. A replication study in an independent cohort of 293 participants with PLA2R-related MN and 285 healthy controls validated these findings. In a joint analysis, a multivariate logistic regression model confirmed that HLA-DRB1*15:01 (odds ratio [OR], 24.9; 95% confidence interval [95% CI], 15.3 to 42.6; P=2.3×10 −35) and HLA-DRB3*02:02 (OR, 17.7; 95% CI, 11.0 to 30.3; P=8.0×10 −29) independently and strongly associated with PLA2R-related MN. As many as 98.7% of patients with PLA2R-related MN, compared with 43.9% of control subjects, carried at least one HLA risk allele. Subjects with either risk allele had higher odds of developing PLA2R-related MN than those without a risk allele (OR, 98.9; 95% CI, 44.4 to 281.7; P=2.5×10 −23). These HLA risk alleles also associated with the age at disease onset in patients with PLA2R-related MN. In conclusion, our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with PLA2R-related MN in the Chinese population.

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          Author and article information

          Journal
          J Am Soc Nephrol
          J. Am. Soc. Nephrol
          jnephrol
          jnephrol
          ASN
          Journal of the American Society of Nephrology : JASN
          American Society of Nephrology
          1046-6673
          1533-3450
          May 2017
          27 December 2016
          : 28
          : 5
          : 1642-1650
          Affiliations
          [* ]National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and
          []BGI-Shenzhen, Shenzhen, China
          Author notes

          W.-B.L. and J.-S.S. contributed equally to the work.

          Correspondence: Prof. Zhi-Hong Liu, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210018, China. Email: Liuzhihong@ 123456nju.edu.cn
          Article
          PMC5407724 PMC5407724 5407724 2016060644
          10.1681/ASN.2016060644
          5407724
          28028136
          275093ff-ff31-4108-b300-5aca43d2912b
          Copyright © 2017 by the American Society of Nephrology
          History
          : 15 June 2016
          : 20 November 2016
          Page count
          Figures: 3, Tables: 1, Equations: 0, References: 32, Pages: 9
          Categories
          Clinical Research
          Custom metadata
          May 2017

          membranous nephropathy,human leukocyte antigen,autoimmune disease,HLA Typing,Target sequencing

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