CDKAL1 gene variants affect the anti-TNF response among Psoriasis patients

Int Immunopharmacol. 2015 Dec;29(2):947-949. doi: 10.1016/j.intimp.2015.11.008. Epub 2015 Nov 10.

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.

Keywords: Anti-TNF; CDKAL1; Gene polymorphism; Psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Cyclin-Dependent Kinase 5 / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Psoriasis / drug therapy*
  • Psoriasis / genetics*
  • Psoriasis / pathology
  • Skin / pathology
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors*
  • tRNA Methyltransferases

Substances

  • Tumor Necrosis Factor Inhibitors
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CDKAL1 protein, human