Common and rare CARD14 gene variants affect the anti-TNF response among Psoriasis patients

Abstract

Background

The CARD14 gene encodes a protein that enhances nuclear factor-kappa B (NF-kB) activation and the upregulation of proinflammatory pathway genes. CARD14 was upregulated in Psoriasis (Psor) vs normal skin, and rare and common CARD14 variants have been associated with the risk of developing Psor. Our hypothesis was that CARD14 variants could also influence the response to anti-TNF therapies among Psor-patients.

Objectives

To determine whether CARD14 gene variants were related with a significant anti-TNF positive response in Psor-patients.

Results

A reduction of at least 75% in the Psoriasis area and severity index (PASI 75) at week 24 was considered as a positive response to treatment. A total of 116 patients (79 responders and 37 non-responders) were next generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (p=0.01; OR=3.71, 95%CI= 1.30-10.51). Furthermore, among responders six patients were heterozygous carriers of the rare p.Glu422Lys and two patients heterozygous for p.Arg682Trp variants (p=0.04).

Conclusions

The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among Psor-patients. In addition, rare CARD14 missense variants could also predispose to a better response.

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