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

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Author

  • L Prokunina
  • C Castillejo-Lopez
  • F Oberg
  • I Gunnarsson
  • L Berg
  • V Magnusson
  • AJ Brookes
  • D Tentler
  • H Kristjansdottir
  • G Grondal
  • AI Bolstad
  • E Svenungsson
  • I Lundberg
  • Gunnar Sturfelt
  • A Jonssen
  • Lennart Truedsson
  • G Lima
  • J Alcocer-Varela
  • R Jonsson
  • UB Gyllensten
  • JB Harley
  • D Alarcon-Segovia
  • K Steinsson
  • ME Alarcon-Riquelme
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Summary, in English

Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women(1-4). 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(5-9). We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families(9,10). Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease(11-14). 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.

Publishing year

2002

Language

English

Pages

666-669

Publication/Series

Nature Genetics

Volume

32

Issue

4

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Microbiology in the medical area
  • Rheumatology and Autoimmunity
  • Immunology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1546-1718