Variants in the 5q31 cytokine gene cluster are associated with psoriasis.

Autor: Chang, M., Li, Y., Yan, C., Callis-Duffin, K. P., Matsunami, N., Garcia, V. E., Cargill, M., Civello, D., Bui, N., Catanese, J. J., Leppert, M. F., Krueger, G. G., Begovich, A. B., Schrodi, S. J.
Předmět:
Zdroj: Genes & Immunity; Mar2008, Vol. 9 Issue 2, p176-181, 6p, 1 Diagram, 2 Charts, 1 Graph
Abstrakt: A multitiered genetic association study of 25 215 single-nucleotide polymorphisms (SNPs) in three case–control sample sets (1446 patients and 1432 controls) identified three IL13-linked SNPs (rs1800925, rs20541 and rs848) associated with psoriasis. Although the susceptibility effects at these SNPs were modest (joint allelic odds ratios (ORs): 0.76 to 0.78; Pcomb: 1.3E−03 to 2.50E−04), the association patterns were consistent across the sample sets, with the minor alleles being protective. Haplotype analyses identified one common, susceptible haplotype CCG (joint allelic OR=1.27; Pcomb=1.88E−04) and a less common, protective haplotype TTT (joint allelic OR=0.74; Pcomb=7.05E−04). In combination with the other known genetic risk factors, HLA-C, IL12B and IL23R, the variants reported here generate an 11-fold psoriasis-risk differential. Residing in the 5q31 cytokine gene cluster, IL13 encodes an important T-cell-derived cytokine that regulates cell-mediated immunity. These results provide the foundation for additional studies required to fully dissect the associations within this cytokine-rich genomic region, as polymorphisms in closely linked candidate genes, such as IRF1, IL5 or IL4, may be driving these results through linkage disequilibrium.Genes and Immunity (2008) 9, 176–181; doi:10.1038/sj.gene.6364451; published online 13 December 2007 [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index