title: Phospholipase A2 receptor (PLA2R1) sequence variants in idiopathic membranous nephropathy.
abstract: The M-type receptor for phospholipase A2 (PLA2R1) is the major target antigen in idiopathic membranous nephropathy (iMN). Our recent genome-wide association study showed that genetic variants in an HLA-DQA1 and phospholipase A2 receptor (PLA2R1) allele associate most significantly with biopsy-proven iMN, suggesting that rare genetic variants within the coding region of the PLA2R1 gene may contribute to antibody formation. Here, we sequenced PLA2R1 in a cohort of 95 white patients with biopsy-proven iMN and assessed all 30 exons of PLA2R1, including canonical (GT-AG) splice sites, by Sanger sequencing. Sixty patients had anti-PLA2R1 in serum or detectable PLA2R1 antigen in kidney tissue. We identified 18 sequence variants, comprising 2 not previously described, 7 reported as rare variants (<1%) in the Single Nucleotide Polymorphism Database or the 1000 Genomes project, and 9 known to be common polymorphisms. Although we confirmed significant associations among 6 of the identified common variants and iMN, only 9 patients had the private or rare variants, and only 4 of these patients were among the 60 who were PLA2R positive. In conclusion, rare variants in the coding sequence of PLA2R1, including splice sites, are unlikely to explain the pathogenesis of iMN.
authors: Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.coenen@gen.umcn.nl
authors: Marieke J H
authors: MJ
authors: Coenen
authors: Julia M
authors: JM
authors: Hofstra
authors: Hanna
authors: H
authors: Debiec
authors: Horia C
authors: HC
authors: Stanescu
authors: Alan J
authors: AJ
authors: Medlar
authors: Bénédicte
authors: B
authors: Stengel
authors: Anne
authors: A
authors: Boland-Augé
authors: Johanne M
authors: JM
authors: Groothuismink
authors: Detlef
authors: D
authors: Bockenhauer
authors: Steve H
authors: SH
authors: Powis
authors: Peter W
authors: PW
authors: Mathieson
authors: Paul E
authors: PE
authors: Brenchley
authors: Robert
authors: R
authors: Kleta
authors: Jack F M
authors: JF
authors: Wetzels
authors: Pierre
authors: P
authors: Ronco
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D056914:Genomic Structural Variation; D015433:Glomerulonephritis, Membranous / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054507:Receptors, Phospholipase A2 / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D054507:Receptors, Phospholipase A2