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| A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans |
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| Author(s): Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdottir H, Grondal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jonssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcon-Segovia D, Steinsson K, Alarcon-Riquelme ME |
| Source: NATURE GENETICS Volume: 32 Issue: 4 Pages: 666-669 Published: DEC 2002 |
| Times Cited: 300 References: 29 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Alarcon-Riquelme, ME (reprint author), Univ Uppsala, Rudbeck Labs, Inst Genet & Pathol, Med Genet Sect, Dag Hammarsjolds Vag 20, S-75185 Uppsala, Sweden |
Addresses:
1. Univ Uppsala, Rudbeck Labs, Inst Genet & Pathol, Med Genet Sect, S-75185 Uppsala, Sweden
2. Everygene AB, Uppsala, Sweden
3. Univ Uppsala, Rudbeck Labs, Inst Genet & Pathol, Sect Pathol, S-75185 Uppsala, Sweden
4. Univ Uppsala, Evolut Biol Ctr, Dept Comparat Physiol, S-75185 Uppsala, Sweden
5. Karolinska Inst, Rheumatol Unit, Stockholm, Sweden
6. Karolinska Inst, Ctr Microbiol & Tumor Biol, Stockholm, Sweden
7. Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden
8. Labdpitalinn, Dept Rheumatol, Reykjavik, Iceland
9. Labdpitalinn, Ctr Rheumatol Res, Reykjavik, Iceland
10. Univ Bergen, Broegelmann Res Lab, Bergen, Norway
11. Haukeland Univ Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway
12. Univ Lund Hosp, Dept Clin Immunol, S-22185 Lund, Sweden
13. Univ Lund Hosp, Dept Rheumatol, S-22185 Lund, Sweden
14. Inst Nacl Ciencias Med & Nutr Salvador Zubirdan, Dept Immunol & Rheumatol, Mexico City, DF Mexico
15. Univ Oklahoma, Dept Med, Arthrit & Immunol Program, Oklahoma Med Res Fdn, Oklahoma City, OK USA
16. US Dept Vet Affairs, Oklahoma City, OK USA |
| Publisher: NATURE AMERICA INC, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 621MH |
| ISSN: 1061-4036 |
| DOI: 10.1038/ng1020 |
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