title: HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy.
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.
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Le
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Shi
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Hua-Zhang
authors.initials: HZ
authors.lastname: Qin
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: ShaoShan
authors.initials: S
authors.lastname: Liang
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yuan-Wei
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Cun-Xia
authors.initials: CX
authors.lastname: Zheng
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Song
authors.initials: S
authors.lastname: Jiang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Wei-Song
authors.initials: WS
authors.lastname: Qin
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; and Liuzhihong@nju.edu.cn.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D059826:HLA-DRB3 Chains / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D054507:Receptors, Phospholipase A2 / Q000502:physiology*; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D054507:Receptors, Phospholipase A2
keywords: HLA Typing; Target sequencing; autoimmune disease; human leukocyte antigen; membranous nephropathy