| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q37.3 | {Systemic lupus erythematosus, susceptibility to, 2} | 605218 | 3 | PDCD1 | 600244 |
A number sign (#) is used with this entry because of evidence that a regulatory polymorphism in the gene encoding programmed cell death-1 (PDCD1; 600244) is the basis of susceptibility to systemic lupus erythematosus (SLE) that maps to chromosome 2q.
For a general phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus, see 152700.
Lindqvist et al. (2000) performed genome scans in families with multiple patients with systemic lupus erythematosus from Iceland and Sweden. Families from each nation generated a significant lod score of greater than 2 for a region of chromosome 2q37 identified by marker D2S125. The lod score for this region among the Icelandic families was 2.06; the lod score among the Swedish families was 2.18. The combination of both family sets gave a highly significant maximum lod score of 4.24 at marker D2S125. This locus is not syntenic to any hitherto described mouse SLE locus.
The gene encoding programmed cell death-1, PDCD1 (600244), lies within the susceptibility region for lupus identified in Nordic multicase families. Prokunina et al. (2002) analyzed 2,510 individuals, including members of 5 independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that they identified in PDCD1. They showed that 1 intronic SNP in PDCD1 (600244.0001) is associated with development of SLE in Europeans (found in 12% of affected individuals vs 5% of controls; relative risk = 2.6) and Mexicans (found in 7% of affected individuals vs 2% of controls; relative risk = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor-1 (RUNX1; 151385) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.
Lindqvist, A.-K. B., Steinsson, K., Johanneson, B., Kristjansdottir, H., Arnasson, A., Grondal, G., Jonasson, I., Magnusson, V., Sturfelt, G., Truedsson, L., Svenungsson, E., Lundberg, I., Terwilliger, J. D., Gyllensten, U. B., Alarcon-Riquelme, M. E. A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q. J. Autoimmun. 14: 169-178, 2000. [PubMed: 10677248] [Full Text: https://doi.org/10.1006/jaut.1999.0357]
Prokunina, L., Castillejo-Lopez, C., Oberg, F., Gunnarsson, I., Berg, L., Magnusson, V., Brookes, A. J., Tentler, D., Kristjansdottir, H., Grondal, G., Bolstad, A. I., Svenungsson, E., and 12 others. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nature Genet. 32: 666-669, 2002. [PubMed: 12402038] [Full Text: https://doi.org/10.1038/ng1020]