A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.

2.50
Hdl Handle:
http://hdl.handle.net/2336/32512
Title:
A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.
Authors:
Prokunina, Ludmila; Castillejo-López, Casimiro; Oberg, Fredrik; Gunnarsson, Iva; Berg, Louise; Magnusson, Veronica; Brookes, Anthony J; Tentler, Dmitry; Kristjansdottir, Helga; Grondal, Gerdur; Bolstad, Anne Isine; Svenungsson, Elisabet; Lundberg, Ingrid; Sturfelt, Gunnar; Jönssen, Andreas; Truedsson, Lennart; Lima, Guadalupe; Alcocer-Varela, Jorge; Jonsson, Roland; Gyllensten, Ulf B; Harley, John B; Alarcón-Segovia, Donato; Steinsson, Kristjan; Alarcon-Riquelme, Marta E
Citation:
Nat. Genet. 2002, 32(4):666-9
Issue Date:
1-Dec-2002
Abstract:
Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified. We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families. Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease. Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P = 0.00001, r.r. (relative risk) = 2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P = 0.0009, r.r. = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/ng1020

Full metadata record

DC FieldValue Language
dc.contributor.authorProkunina, Ludmila-
dc.contributor.authorCastillejo-López, Casimiro-
dc.contributor.authorOberg, Fredrik-
dc.contributor.authorGunnarsson, Iva-
dc.contributor.authorBerg, Louise-
dc.contributor.authorMagnusson, Veronica-
dc.contributor.authorBrookes, Anthony J-
dc.contributor.authorTentler, Dmitry-
dc.contributor.authorKristjansdottir, Helga-
dc.contributor.authorGrondal, Gerdur-
dc.contributor.authorBolstad, Anne Isine-
dc.contributor.authorSvenungsson, Elisabet-
dc.contributor.authorLundberg, Ingrid-
dc.contributor.authorSturfelt, Gunnar-
dc.contributor.authorJönssen, Andreas-
dc.contributor.authorTruedsson, Lennart-
dc.contributor.authorLima, Guadalupe-
dc.contributor.authorAlcocer-Varela, Jorge-
dc.contributor.authorJonsson, Roland-
dc.contributor.authorGyllensten, Ulf B-
dc.contributor.authorHarley, John B-
dc.contributor.authorAlarcón-Segovia, Donato-
dc.contributor.authorSteinsson, Kristjan-
dc.contributor.authorAlarcon-Riquelme, Marta E-
dc.date.accessioned2008-07-18T16:40:47Z-
dc.date.available2008-07-18T16:40:47Z-
dc.date.issued2002-12-01-
dc.date.submitted2008-07-18-
dc.identifier.citationNat. Genet. 2002, 32(4):666-9en
dc.identifier.issn1061-4036-
dc.identifier.pmid12402038-
dc.identifier.doi10.1038/ng1020-
dc.identifier.urihttp://hdl.handle.net/2336/32512-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractSystemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified. We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families. Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease. Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P = 0.00001, r.r. (relative risk) = 2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P = 0.0009, r.r. = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.en
dc.language.isoenen
dc.publisherNature Pub. Co.en
dc.relation.urlhttp://dx.doi.org/10.1038/ng1020en
dc.subject.mesh3' Untranslated Regionsen
dc.subject.meshAllelesen
dc.subject.meshAmino Acid Substitutionen
dc.subject.meshAntigens, CDen
dc.subject.meshAntigens, Surfaceen
dc.subject.meshApoptosis Regulatory Proteinsen
dc.subject.meshBase Sequenceen
dc.subject.meshCell Extractsen
dc.subject.meshCell Nucleusen
dc.subject.meshFemaleen
dc.subject.meshGene Frequencyen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHaplotypesen
dc.subject.meshHumansen
dc.subject.meshJurkat Cellsen
dc.subject.meshLeukocytes, Mononuclearen
dc.subject.meshLinkage Disequilibriumen
dc.subject.meshLod Scoreen
dc.subject.meshLupus Erythematosus, Systemicen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshPolymorphism, Geneticen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshPromoter Regions (Genetics)en
dc.subject.meshTandem Repeat Sequencesen
dc.subject.meshTranscription Factorsen
dc.titleA regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.en
dc.typeArticleen
dc.contributor.departmentInstitute of Genetics & Pathology, Section for Medical Genetics, Rudbeck Laboratories, University of Uppsala, Dag Hammarsjölds väg 20, 751 85, Uppsala, Sweden.en
dc.identifier.journalNature geneticsen

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