New polymorphisms associated with response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis.
Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20-30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.
Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
R
R
Prieto-Pérez
Dermatology Service, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
G
G
Solano-López
Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
T
T
Cabaleiro
Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
M
M
Román
Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
D
D
Ochoa
Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
M
M
Talegón
Dermatology Service, Hospital Universitario Gregorio Marañón, Madrid, Spain.
O
O
Baniandrés
Dermatology Service, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
J L
JL
López-Estebaranz
Dermatology Service, Hospital Universitario Infanta Leonor, Madrid, Spain.
P
P
de la Cueva
Dermatology Service, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
E
E
Daudén
Clinical Pharmacology Service, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, University Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
F
F
Abad-Santos
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003879:Dermatologic Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D015415:Biomarkers; D003879:Dermatologic Agents; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
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