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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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
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
LU publication?
yes
id
ada7db0a-aab0-4645-990e-1c470f2248d5 (old id 322191)
date added to LUP
2016-04-01 16:52:33
date last changed
2022-04-23 00:55:04
@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}},
  doi          = {{10.1038/ng1020}},
  volume       = {{32}},
  year         = {{2002}},
}