Table 1.
Pharmacogenetics studies on ustekinumab showing significant associations between polymorphisms and response to treatment. SNP: single nucleotide polymorphism, HLA: human leukocyte antigens, PASI: Psoriasis Area and Severity Index, IL: interleukin * Therapeutic success increases in HLA-C*06:02 positive patients.
| Reference | Genes | Protein Function | Allele/SNP | Response | Number of Patients | Country | Weeks after Initiation of Treatment | Outcome Measure |
|---|---|---|---|---|---|---|---|---|
| Talamonti et al, 2013 [53] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 51 | Italy | 4, 12, 28 and 40 | PASI 75. PASI 90 |
| Chiu et al, 2014 [63] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 66 | China | 16 and 28 | PASI50, PASI75, PASI90 |
| Prieto-Pérez et al, 2015 [65] | IL-17F | This cytokine is expressed by activated T cells, and is involved, among others, in IL-23 and IL-17 Family Signaling Pathways in the immune response. | rs763780 (TC genotype) | Worse | 70 | Spain | 12 and 24 | PASI75 |
| Masouri et al, 2016 [35] | ERAP1 | Aminopeptidase involved in trimming precursors of HLA class I-binding peptides to allow their presentation by MHC class I molecules | rs151823 (CC genotype) | Better | 22 | Greece | 24 | PASI 50, PASI75 |
| rs26653 (GG genotype) | Better | |||||||
| Li et al, 2016 [56] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 601 | The United States of America | 4, 12, 24 and 28 | PASI50, PASI75, PASI 90.PASI100 |
| Galluzo et al, 2016 [57] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 64 | Italy | 4, 12, 28, 40 and 52 | PASI 75 |
| Talamonti et al, 2016 [54] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 134 | Italy | 4, 12, 28, 52, 76, 104, 156 | PASI75 |
| Talamonti et al, 2017 [55] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 255 | Italy | 4, 12, 28, 40 and 52 | PASI 50, PASI75, PASI90 |
| Raposo et al, 2017 [58] | HLA-C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better | 116 | Portugal | 4, 12, 24 and 52 | PASI75 |
| Reek et al, 2017 [64] | IL12b | Subunit of interleukin 12, expressed by activated macrophages and essential inducer of Th1 cell development. | rs3213094 (CT genotype) | Better | Number of patients not stated. Sixty-six episodes on ustekinumab | The Netherlands | 6, 12, and every three months thereafter | PASI75, ΔPASI |
| TNFAIP3 | Zinc finger protein and ubiquitin-editing enzyme. | rs610604 (GG genotype) | Worse | |||||
| Prieto-Pérez et al, 2017 [61] | TNFRSF1A | Member of the TNF receptor superfamily of proteins. Plays a role in cell survival, apoptosis, and inflammation. | rs191190 (TT genotype) | Worse | 69 | Spain | 16 | PASI75 |
| HTR2A | Serotonin receptor. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder. | rs6311 (TT genotype) | Worse | |||||
| NFKBIA | Member of the NF-kappa-B inhibitor family. | rs2145623 (CC genotype) | Worse | |||||
| ADAM33 | Member of the ADAM (a disintegrin and metalloprotease domain) family. | rs2787094 (CC genotype) | Worse | |||||
| IL13 | Immunoregulatory cytokine produced primarily by activated Th2 cells. | rs848 (TT genotype) | Worse | |||||
| CHUK | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway. | rs11591741 (GC genotype) | Better | |||||
| C17orf51 | RNA Gene associated with psoriasis | rs1975974 (AG genotype) | Better | |||||
| ZNF816A | Transcriptional regulation | rs9304742 (CT genotype) | Better | |||||
| STAT4 | Mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. | rs7574865 (GT genotype) | Better | |||||
| SLC22A4 | Polyspecific organic cation transporter critical for elimination of drugs and environmental toxins. | rs1050152 (CT genotype) | Better | |||||
| C9orf72 | Important role in the regulation of endosomal trafficking. Interacts with Rab proteins, which are involved in autophagy and endocytic transport. | rs774359 (CT genotype) | Better | |||||
| Loft et al, 2018 [24] | IL1B | Important mediator of the inflammatory response. | rs1143623 (G/C genotype) | Better | 230 | Denmark | 12, 24 | PASI50, PASI75 |
| rs1143627 (T/C genotype) | Better | |||||||
| TIRAP | TIR adaptor protein involved in the toll-like receptor signaling pathway in the immune system. | rs8177374 (C/T genotype) | Better | |||||
| TLR5 | Member of the TLR family, which plays a fundamental role in pathogen recognition and activation of the innate immune response. | rs5744174 (T/C genotype) | Better | |||||
| Il12B | Subunit of interleukin 12. This cytokine is expressed by activated macrophages and is an essential inducer of Th1 cells development. | rs6887695 (GG genotype) | Better* | |||||
| rs3212227 (absence of AA genotype) | Better* | |||||||
| Dand et al, 2019 [51] | HLA- C | It belongs to the HLA class I heavy chain group. Relevant role in the immune system as it helps to present endoplasmic reticulum peptides. | HLA-C*06:02 positive | Better. | 487 | The United Kingdom | 12, 24, 48 | PASI 75, PASI90, PASI100 |