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


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.

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@article{Prokunina2002ARP, title={A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.}, author={Ludmila Prokunina and Casimiro Castillejo-L{\'o}pez and Fredrik Oberg and Iva Gunnarsson and Louise Berg and Veronica Magnusson and Anthony J Brookes and Dmitry Tentler and Helga Kristjansd{\'o}ttir and Gerdur Gr{\"{o}ndal and Anne Isine Bolstad and Elisabet Svenungsson and Ingrid Lundberg and Gunnar Sturfelt and Andreas J{\"{o}nssen and Lennart Truedsson and Guadalupe Lima and Jorge Alcocer-Varela and Roland Jonsson and Ulf B Gyllensten and John B Harley and Donato Alarc{\'o}n-Segovia and Kristj{\'a}n Steinsson and Marta E Alarc{\'o}n-Riquelme}, journal={Nature genetics}, year={2002}, volume={32 4}, pages={666-9} }