Scientists at the University of Michigan have linked four genes immune responses to psoriasis: IL23A, TNFAIP3, TNIP1, and pair IL3 and IL13.
Within the past 18 months, researchers worldwide have increased the number of loci associated with psoriasis from one to 10. This study is the first to identify changes in the IL23A gene in psoriasis patients, though two of the previously identified psoriasis genes (IL12B and IL23R) encode proteins that bind to IL23A protein. Variations in the structure of any of these three genes may predispose people to chronic immune responses that ultimately result in psoriasis, the researchers suggest.
The team also found two genes activated by TNF-alpha, TNFAIP3 and TNIP1,that show patterns distinct from those in healthy controls. Together, these genes limit immune responses, so alterations in them may allow immune systems to work too well, the scientists explain. Variants of TNFAIP3 also have been associated with rheumatoid arthritis and lupus.
The fourth hotspot implicates a pair of genes, IL4 and IL13. These genes support development of Th2 cells, a type of immune system T cell. Any condition that leads to too few or too many Th2 cells in relation to other types of T cells may result in disease, the investigators says.
The team began by looking for SNPs at 438,670 sites in 1,359 psoriasis cases and 1,400 healthy controls. Initial scans signaled differences in at least three previously identified DNA sites, with HLA-Cw6 producing the strongest genetic signal.
They then expanded the study to look at 18 of the most interesting loci in an additional 5,048 cases and 5,051 controls. In all, seven of the 18 loci showed consistently strong association with psoriasis.
The study appears in the January issue of Nature Genetics.