The relationship between tumour necrosis factor (TNF)-α promoter and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-α therapy in psoriasis: a case-control study

BackgroundAntitumour necrosis factor (anti-TNF)- agents can be used successfully to treat patients with psoriasis and other inflammatory diseases. However, very few studies have examined the relationship between TNF- polymorphisms and the response to anti-TNF- agents. ObjectivesTo study the association of single nucleotide polymorphisms (SNPs) of the TNF- promoter and IL12B/IL23R genes with the response to anti-TNF- in patients with psoriasis. MethodsSNPs for the TNF- promoter and IL12B/IL23R genes, and the presence of the HLA-Cw6 haplotype were genotyped for 109 patients. We studied the association between these SNPs and the efficacy of treatment at 3 and 6months [Psoriasis Area and Severity Index (PASI) and body surface area (BSA)]. ResultsPatients with the TNF--238GG genotype more frequently achieved a PASI75 at 6months (82<bold>5</bold>% vs. 58<bold>8</bold>%, P=0<bold>049</bold>). At 6months, patients with the TNF--857CT/TT genotypes showed greater improvements in PASI score and BSA (83<bold>1</bold>% vs. 92<bold>7</bold>%, P=0<bold>004</bold>; 82<bold>7</bold>% vs. 92<bold>6</bold>%, P=0<bold>009</bold>) and more frequently achieved PASI75 (71<bold>4</bold>% vs. 96<bold>3</bold>%, P=0<bold>006</bold>). More patients with the TNF--1031TT genotype achieved PASI75 at 3months (90<bold>8</bold> vs. 75<bold>7</bold>, P=0<bold>047</bold>) and 6months (85<bold>5</bold>% vs. 65<bold>7</bold>%, P=0<bold>038</bold>) and demonstrated superior improvements in PASI at 6months (89<bold>9</bold>% vs. 78<bold>7</bold>%, P=0<bold>041</bold>). Patients with the IL23R-GG genotype (rs11209026) achieved PASI90 at 6months more frequently (66<bold>3</bold>% vs. 0, P=0<bold>006</bold>) and the improvement of the PASI score was also greater (86<bold>8</bold>% vs. 67<bold>8</bold>%, P=0<bold>013</bold>). Patients with the HLA-Cw6 haplotype showed poorer response than those without this haplotype. ConclusionThis study identified a relationship between certain TNF- and IL12B/IL23R polymorphisms and the short-term response to anti-TNF- drugs. If these results are confirmed, this information will allow for stratified consent with more accurate prediction of response/personalized choice of treatment hierarchy for the patient.