title: CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients.
abstract: The heterogeneous response to anti-TNF biological drugs among Psoriasis (Psor) patients might be explained by gene variants linked to the risk for Psor. Common variants in the CDKAL1 gene have been associated with the risk of developing Psor. Our hypothesis was that these variants could also influence the response to anti-TNFs among Psor-patients. A reduction of at least 75% in the Psoriasis area and severity index (PASI 75) at week 24 was considered a positive response to treatment. A total of 116 patients (78 responders and 38 non-responders) were genotyped for the CDKAL1 rs6908425, rs4712523, rs111739077, and rs77152992 (p.P409L) single nucleotide polymorphisms. Allele and genotype frequencies differed between the two response groups, with the highest difference for the rs6908425: CC homozygotes were significantly more common among responders (72% vs. 45%; p=0.005; OR=3.14, 95%CI=1.40-7.05). In conclusion, our data suggested that CDKAL1 gene variants have a significant effect on the response to anti-TNF therapies among Psor patients. If confirmed on other large cohorts of patients, the genotyping of these variants might help to predict the biological response.
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain; Departamento Medicina, Universidad Oviedo, Oviedo; Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Coto-Segura
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Batalla
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: González-Fernández
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez
authors.affiliation: Dermatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Santos-Juanes
authors.affiliation: Reumatología, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Queiro
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Iglesias
authors.affiliation: Genética Molecular, Hospital Universitario Central Asturias, Oviedo, Spain; Departamento Medicina, Universidad Oviedo, Oviedo; Spain. Electronic address: eliecer.coto@sespa.es.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000328:Adult; D000483:Alleles; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D012867:Skin / Q000473:pathology; D016896:Treatment Outcome; D000079424:Tumor Necrosis Factor Inhibitors; D012359:tRNA Methyltransferases
chemical_list: D000079424:Tumor Necrosis Factor Inhibitors; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human
keywords: Anti-TNF; CDKAL1; Gene polymorphism; Psoriasis