Article

Detailed genetic characterization of the interleukin-23 receptor in psoriasis.

Celera, 1401 Harbor Bay Parkway, Alameda, CA, USA.
Genes and immunity (impact factor: 4.22). 09/2008; 9(6):546-55. DOI:10.1038/gene.2008.55 pp.546-55
Source: PubMed

ABSTRACT Using a multi-tiered, case-control association design, scanning 25 215 gene-centric SNPs, we previously identified two psoriasis susceptibility genes: IL12B and IL23R. These results have recently been confirmed. To better characterize the IL23R psoriasis-association, we used a fine mapping strategy to identify 59 additional IL23R-linked SNPs, which were genotyped in our three independent, white North American sample sets (>2800 individuals in toto). A sliding window of haplotype association demonstrates colocalization of psoriasis susceptibility effects within the boundaries of IL23R across all sample sets, thereby decreasing the likelihood that neighboring genes, particularly IL12RB2, are driving the association at this region. Additional haplotype work identified two 5-SNP haplotypes with strong protective effects, consistent across our three sample sets (OR(common)=0.67; P(comb)=4.32E-07). Importantly, heterogeneity of effect was extremely low between sample sets for these haplotypes (P(Het)=0.961). Together, these protective haplotypes attain a frequency of 16% in controls, declining to 11% in cases. The characterization of association patterns within IL23R to specific predisposing/protective variants will play an important role in the elucidation of psoriasis etiology and other related phenotypes. Further, this work is essential to lay the foundation for the role of IL23R genetics in response to pharmaceutical therapy and dosage.

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    Article: Biology of interleukin-22.
    Kerstin Wolk, Ellen Witte, Katrin Witte, Katarzyna Warszawska, Robert Sabat
    [show abstract] [hide abstract]
    ABSTRACT: Interleukin (IL)-22 is a member of the IL-10 family of cytokines and represents an important effector molecule of activated Th22, Th1, and Th17 cells, as well as Tc-cell subsets, gammadelta T cells, natural killer (NK), and NKT cells. IL-22 mediates its effects via a heterodimeric transmembrane receptor complex consisting of IL-22R1 and IL-10R2 and subsequent Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathways including Jak1, Tyk2, and STAT3. Whereas in some aspects, IL-22 acts synergistically with tumor necrosis factor-alpha, IL-1beta, or IL-17, most functions of IL-22 are unique. Importantly, IL-22 does not serve the communication between immune cells. It mainly acts on epithelial cells and hepatocytes, where it favors the antimicrobial defense, regeneration, and protection against damage and induces acute phase reactants and some chemokines. This chapter illuminates in detail the properties of IL-22 with respect to its gene, protein structure, cellular sources, receptors, target cells, biological effects, and, finally, its role in chronic inflammatory diseases, tumors, and infection.
    Seminars in Immunopathology 03/2010; 32(1):17-31. · 6.27 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

5-SNP haplotypes
 
59 additional IL23R-linked SNPs
 
Additional haplotype work
 
characterization
 
dosage
 
haplotype association
 
haplotypes
 
IL23R genetics
 
IL23R psoriasis-association
 
neighboring genes
 
pharmaceutical therapy
 
protective haplotypes
 
psoriasis etiology
 
sample sets
 
scanning 25 215 gene-centric SNPs
 
sliding window
 
specific predisposing/protective variants
 
three independent
 
three sample sets
 
white North American sample sets
 

V E Garcia