DO: 9074;
Cytogenetic location: 1q21-q23 Genomic coordinates (GRCh38): 1:143,200,001-165,500,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q21-q23 | {Systemic lupus erythematosus, susceptibility to, 14} | 613145 | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Relative deficiency of pentraxin proteins is implicated in the pathogenesis of SLE. The C-reactive protein (CRP; 123260) response is defective in patients with acute flares of disease, and mice with targeted deletions of the APCS (104770) gene develop a lupus-like illness. In humans, the CRP and APCS genes are both within the chromosome 1q23-q24 interval that has been linked to SLE. Among 586 simplex SLE families, Russell et al. (2004) found that basal levels of CRP were influenced independently by a synonymous change at codon 144 designated CRP2 (rs1800947) and a 3-prime flanking region SNP designated CRP4 (rs1205), and the latter was associated with SLE and antinuclear autoantibody production. Russell et al. (2004) hypothesized that defective disposal of potentially immunogenic material may be a contributory factor in lupus pathogenesis.
Edberg et al. (2008) analyzed SNPs in the proximal 5-prime promoter region of the CRP gene on chromosome 1q21-q23 in SLE patients and controls and found the strongest association for -707A-G (CRP-707, rs3093061; corrected p = 8.75 x 10(-5) and 2.66 x 10(-5) for Caucasian and African American case-control samples, respectively). The authors noted that linkage disequilibrium (LD) exists between SNPs in the proximal promoter, but that association of functional haplotypes containing CRP-409/CRP-390 (-409G-A, rs3091244; -390C-T-A, rs3093062) appeared to be driven by the CRP-707 association; however, they also noted CRP-707 is not predicted to lie within a transcription factor-binding site. There was also a high degree of LD between the promoter SNPs studied by Edberg et al. (2008) and CRP2 and CRP4, which the authors suggested might explain the previously reported association between the latter SNPs and CRP levels.
Edberg, J. C., Wu, J., Langefeld, C. D., Brown, E. E., Marion, M. C., McGwin, G., Jr., Petri, M., Ramsey-Goldman, R., Reveille, J. D., Frank, S. G., Kaufman, K. M., Harley, J. B., Alarcon, G. S., Kimberly, R. P. Genetic variation in the CRP promoter: association with systemic lupus erythematosus. Hum. Molec. Genet. 17: 1147-1155, 2008. [PubMed: 18182444] [Full Text: https://doi.org/10.1093/hmg/ddn004]
Russell, A. I., Cunninghame Graham, D. S., Shepherd, C., Roberton, C. A., Whittaker, J., Meeks, J., Powell, R. J., Isenberg, D. A., Walport, M. J., Vyse, T. J. Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus. Hum. Molec. Genet. 13: 137-147, 2004. [PubMed: 14645206] [Full Text: https://doi.org/10.1093/hmg/ddh021]