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

Prokunina, L; Castillejo-Lopez, C; Oberg, F; Gunnarsson, I; Berg, L; Magnusson, V; Brookes, AJ; Tentler, D; Kristjansdottir, H and Grondal, G, et al. (2002) In Nature Genetics 32(4). p.666-669
Abstract
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... (More)
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. (Less)
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Nature Genetics
volume
32
issue
4
pages
666 - 669
publisher
Nature Publishing Group
external identifiers
  • pmid:12402038
  • wos:000179593000022
  • scopus:13244277850
ISSN
1546-1718
DOI
10.1038/ng1020
language
English
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yes
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ada7db0a-aab0-4645-990e-1c470f2248d5 (old id 322191)
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2007-11-09 08:07:57
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@article{ada7db0a-aab0-4645-990e-1c470f2248d5,
  abstract     = {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.},
  author       = {Prokunina, L and Castillejo-Lopez, C and Oberg, F and Gunnarsson, I and Berg, L and Magnusson, V and Brookes, AJ and Tentler, D and Kristjansdottir, H and Grondal, G and Bolstad, AI and Svenungsson, E and Lundberg, I and Sturfelt, Gunnar and Jonssen, A and Truedsson, Lennart and Lima, G and Alcocer-Varela, J and Jonsson, R and Gyllensten, UB and Harley, JB and Alarcon-Segovia, D and Steinsson, K and Alarcon-Riquelme, ME},
  issn         = {1546-1718},
  language     = {eng},
  number       = {4},
  pages        = {666--669},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans},
  url          = {http://dx.doi.org/10.1038/ng1020},
  volume       = {32},
  year         = {2002},
}