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Article: Risk HLA-DQA1 and PLA2R1 alleles in idiopathic membranous nephropathy

TitleRisk HLA-DQA1 and PLA2R1 alleles in idiopathic membranous nephropathy
Authors
Issue Date2011
Citation
New England Journal of Medicine, 2011, v. 364 n. 7, p. 616-626 How to Cite?
AbstractBACKGROUND: Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population. METHODS: We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method). RESULTS: In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A2 receptor (PLA2R1) (SNP rs4664308, P = 8.6×10-29), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P = 8.0×10-93). The association with HLA-DQA1 was significant in all three populations (P = 1.8×10-9, P = 5.6×10×, and P = 5.2×10 -36 in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2). CONCLUSIONS: An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA. Copyright © 2011 Massachusetts Medical Society.
Persistent Identifierhttp://hdl.handle.net/10722/195495
ISSN
2015 Impact Factor: 59.558
2015 SCImago Journal Rankings: 14.619
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorStanescu, HC-
dc.contributor.authorArcos-Burgos, M-
dc.contributor.authorMedlar, A-
dc.contributor.authorBockenhauer, D-
dc.contributor.authorKottgen, A-
dc.contributor.authorDragomirescu, L-
dc.contributor.authorVoinescu, C-
dc.contributor.authorPatel, N-
dc.contributor.authorPearce, K-
dc.contributor.authorHubank, M-
dc.contributor.authorStephens, HAF-
dc.contributor.authorLaundy, V-
dc.contributor.authorPadmanabhan, S-
dc.contributor.authorZawadzka, A-
dc.contributor.authorHofstra, JM-
dc.contributor.authorCoenen, MJH-
dc.contributor.authorDen Heijer, M-
dc.contributor.authorKiemeney, LALM-
dc.contributor.authorBacq-Daian, D-
dc.contributor.authorStengel, B-
dc.contributor.authorPowis, SH-
dc.contributor.authorBrenchley, P-
dc.contributor.authorFeehally, J-
dc.contributor.authorRees, AJ-
dc.contributor.authorDebiec, H-
dc.contributor.authorWetzels, JFM-
dc.contributor.authorRonco, P-
dc.contributor.authorMathieson, PW-
dc.contributor.authorKleta, R-
dc.date.accessioned2014-02-28T06:12:14Z-
dc.date.available2014-02-28T06:12:14Z-
dc.date.issued2011-
dc.identifier.citationNew England Journal of Medicine, 2011, v. 364 n. 7, p. 616-626-
dc.identifier.issn0028-4793-
dc.identifier.urihttp://hdl.handle.net/10722/195495-
dc.description.abstractBACKGROUND: Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population. METHODS: We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method). RESULTS: In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A2 receptor (PLA2R1) (SNP rs4664308, P = 8.6×10-29), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P = 8.0×10-93). The association with HLA-DQA1 was significant in all three populations (P = 1.8×10-9, P = 5.6×10×, and P = 5.2×10 -36 in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2). CONCLUSIONS: An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA. Copyright © 2011 Massachusetts Medical Society.-
dc.languageeng-
dc.relation.ispartofNew England Journal of Medicine-
dc.titleRisk HLA-DQA1 and PLA2R1 alleles in idiopathic membranous nephropathy-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1056/NEJMoa1009742-
dc.identifier.pmid21323541-
dc.identifier.scopuseid_2-s2.0-79951827439-
dc.identifier.volume364-
dc.identifier.issue7-
dc.identifier.spage616-
dc.identifier.epage626-
dc.identifier.isiWOS:000287406000007-
dc.identifier.f10009091961-

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