Genetics of Psoriasis and Pharmacogenetics of Biological Drugs
Table 1
Single-nucleotide polymorphisms (SNPs) in genes associated with psoriasis.
Gene
Role in immune system*
SNP
MAF**
Minor allele
Population
References
IL23R
Encodes a subunit of the receptor required for IL23A signaling. This protein associates constitutively with JAK2 and binds to transcription activator STAT3
Encodes a cytokine produced by monocytes and lymphocytes that downregulates the expression of Th1 cytokines and blocks NF-B activity. It enhances B-cell survival, proliferation, and antibody production and regulates the JAK-STAT signaling pathway
Encodes a proinflammatory cytokine produced by macrophages. TNFα is implicated in multiple roles such as cell proliferation, differentiation, and apoptosis
Encodes a cytokine produced by activated Th2 that is involved in maturation and differentiation of B cells. IL13 downregulates macrophage activity and inhibits the production of proinflammatory cytokines and chemokines
TNF induces the expression of TNFAIP3, which inhibits NF-B activation and TNF-mediated apoptosis. TNFAIP3 is involved in cytokine-mediated immune and inflammatory responses
Encodes a member of the NF-B inhibitor family, which interacts with REL dimers to inhibit NF-B/REL complexes, which are involved in inflammatory responses
IL4 is a pleiotropic cytokine involved in the modulation of Th2 immune responses. IL4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13
Encodes a cytokine that regulates T-cell and natural killer activation and proliferation. IL15 also induces the activation of JAK kinases, as well as the phosphorylation and activation of STAT3, STAT5, and STAT6
In response to cytokines, the STAT proteins are phosphorylated and translocate to the cell nucleus, where they act as transcription activators. STAT transduces IL12, IL23, and IFN type I signals in T lymphocytes and regulates the differentiation of Th cells
Encodes a protein that interacts with TRAF proteins and plays a central role in innate immunity in response to pathogens, inflammatory signals, and stress
Encodes a member of the JAK protein family that promulgate cytokine signals by phosphorylating receptor subunits. TYK2 is a component of IFN I and II signaling pathways and may play a role in antiviral immunity
Data from NCBI web page [57]; MAF: minor allele frequency for Caucasian population (data from HapMap web page [106] and Alfred [107]). IL: interleukin; R: receptor; JAK: Janus kinase; STAT: signal transducer and activator of transcription; Th1: type 1 helper T lymphocyte; TNF: tumor necrosis factor; GBP: guanylate-binding protein; GTP: guanosine triphosphate; GDP: guanosine diphosphate; GMP: guanosine monophosphate; TNFAIP: TNF-alpha interacting protein; TNIP1: TNFAIP3 interacting protein; IL1RN: interleukin 1 receptor antagonist; HLA: human leukocyte antigen; NF-BIA: nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha; REL: v-rel reticuloendotheliosis viral oncogene; APOE: apolipoprotein E; VDR: vitamin D receptor; TNFRSF1: tumor necrosis factor receptor superfamily; MCP: monocyte chemoattractant protein; CTLA4: cytotoxic T lymphocyte-associated protein 4; DEFB4: defensin beta 4A; IFN: interferon; ERAP: endoplasmic reticulum aminopeptidase; TRAF3IP: TRAF3 (TNF receptor-associated factor 3) interacting protein; IRAK: interleukin-1 receptor-associated kinase; TYK: tyrosine kinase; IFIH1: interferon induced with helicase C domain 1; LCE: late cornified envelope; RNF114: ring finger protein 114; association between psoriasis and response to anti-TNF treatment; haplotype GG of rs3087243-rs231775 associated with psoriasis.