Several observational studies have assessed the association between psoriasis, psoriatic arthritis (PsA) and type 2 diabetes mellitus, with inconclusive results. We set out to investigate the association between psoriasis, PsA and type 2 diabetes mellitus. Observational studies assessing the relationship between psoriasis or PsA and type 2 diabetes mellitus up to December 2012 were identified by electronic and hand searches in Medline, Embase, PubMed, the Cochrane Database of Systematic Reviews and Google Scholar. For each study we collected the first author's last name, publication year, country of origin, study design, characteristics of participants (sample size, age and sex), the variables incorporated into the multivariable analyses, and the odds ratios (ORs) of psoriasis associated with diabetes along with the corresponding 95% confidence intervals (CIs). From the data provided in each article, the crude OR was also calculated. Forty-four observational studies (in 37 articles) were identified for the final analysis. The pooled OR from random-effects analysis was determined to be 1·76 (95% CI 1·59-1·96). The highest risk was for patients suffering from PsA (OR 2·18, 95% CI 1·36-3·50). We also observed a dose effect in the risk of suffering from type 2 diabetes mellitus, as patients considered as having severe psoriasis had higher risk (OR 2·10, 95% CI 1·73-2·55) than the pooled OR. We perform meta-regression and sensitivity analyses to explore sources of heterogeneity among the studies and to determine how they would influence the estimates, and found no significant influence in the results of the meta-analyses. The findings support the association between psoriasis, PsA and type 2 diabetes mellitus. Some caution must be taken in the interpretation of these results because there may be heterogeneity between studies.

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Genetic factors are involved not only in the overall risk of suffering psoriasis, but also in their clinical characteristics and eventually in drug outcome. Biological therapies have dramatically improved the prognosis of Psoriasis. However, these treatments are very expensive and patients often exhibit a heterogeneous response that could be partially attributed to their genetic background. Thus, the research for genetic markers in psoriatic patients that could predict a poor response to biological therapies is an important issue. Our aim was to evaluate the effect of DNA variants at the "TNFα pathway" that could affect the risk of developing Psoriasis or the response to biological therapies among these patients. The genetic association study included a total of 518 Psoriatic patients and 480 healthy controls. Ninety of these patients received biological treatment and based on the change in the PASI score after 24 weeks were classified as good (PASI score ≥75%), intermediate (PASI 50-75), and non-responders (PASI <50). Next generation sequencing (NGS) with semiconductor-array technology was used to identify the nucleotide variants in the TNF α, TNFRSF1A and TNFRSF1B, and we only found three missense amino acid changes, all in TNFRSF1B. Interestingly, we found a significantly higher frequency of rs1061622 G carriers among CW6-positive patients (p = 0.004; OR = 1.69, 95% CI = 1.18-2.41). Allele G (p.196R) carriers were significantly more frequent in the non-responder group (56%) (p = 0.05). In conclusion, we report a significant association between the TNFRSF1B p.M196R variant and the risk for psoriasis and the response to treatment with anti-TNF or anti-Il-12/Il-23. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.

A recent genomic survey identified the association between a common single nucleotide polymorphism (SNP) at the CARD14 gene (SNP rs11652075; p.Arg820Trp) and psoriasis (Psor). Our aim was to replicate the association between this polymorphism and to determine whether other CARD14 variants could explain the association. A total of 400 Psor patients (mean age 47±15; 55% male) and 420 healthy controls (mean age 51±16; 56% male) all Caucasian were genotyped for rs11652075. The rs11652075 CC genotype was significantly associated with Psor in our population (p=0.003; odds ratios=1.59; 95% confidence intervals=1.16-2.19; statistical power >80). The sequencing of the whole CARD14 coding exons in a total of 15 patients did not identify other DNA variants that could explain this association. We did not find significant differences (allele/genotype frequencies) between the patients according to disease severity, presence of arthritis, onset of age, and family history of Psor. We confirmed the association between SNP rs11652075 at the CARD14 gene and Psor. The absence of other coding variants among our patients supported a direct role for this missense polymorphism on Psor risk.

Our aim was to determine whether the HLA-Cw6 and late-cornified envelope (LCE) deletion polymorphisms were related to disease improvement among psoriasis patients treated with anti-tumor necrosis factor (TNF) antibodies. The study included a total of 116 patients. Positive response (68%) was defined as a reduction of at least 75% of the Psoriasis Area and Severity Index (PASI) after 24 weeks of starting the anti-TNF therapy. We found a trend toward a better response among Cw6-positive patients. The frequency of patients who did not reach the PASI75 was higher among the LCE-DD patients (P=0.028; odds ratio=2.45, 95% confidence interval=1.09-5.52). Patients who were Cw6-positive and LCE-I carriers (ID/II) were significantly more likely to reach PASI75 than those who were Cw6-negative and LCE-DD (P=0.034; odds ratio=3.14, 95% confidence interval=1.07-9.24). In conclusion, we found an interaction between the HLA-Cw6 and LCE genotypes on disease improvement among psoriatic patients treated with anti-TNFs.

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