###### Abstract  
Background: Psoriasis can present different phenotypes and could affect diverse body areas. In contrast to the high effectiveness of biological drugs in the treatment of trunk and extremities plaque psoriasis, in palmoplantar phenotypes and in plaque scalp psoriasis, these same drugs usually have reduced efficacy. Anti-TNF drugs could induce the appearance of palmoplantar pustulosis (PPP) in patients with other inflammatory diseases. The objective of this study is to identify if there are DNA Copy Number Variations (CNVs) associated with these different clinical phenotypes, which could justify the differences found in clinical practice. Moreover, we intend to elucidate if anti-TNF-induced PPP has a similar genetic background to idiopathic PPP. Methods: Skin samples were collected from 39 patients with different patterns of psoriasis and six patients with anti-TNF-induced PPP. The CNVs were obtained from methylation array data (Illumina Infinium Human Methylation) using the conumee R package. Results: No significant CNVs were found between the different phenotypes and the locations of psoriasis compared. Nevertheless, we found two significant bins harboring five different genes associated with anti-TNF-induced PPP in patients with a different background other than psoriasis. Conclusions: Our results may help to predict which patients could develop anti-TNF-induced PPP. pharmacogenomics; psoriasis genetics methylation array; biological drugs; adverse effect prediction +
Footnote †: journal: Personalized Medicine  
can be limited exclusively to the scalp, palms, and soles with or without the presence of the typical psoriasis Vulgaris plaques. The palmoplantar forms can manifest as erythematosusous-scaly-hyperkeratotic plaques (hyperkeratotic palmoplantar psoriasis) or as sterile pustules (palmoplantar pustular psoriasis-PPP). In contrast to the high effectiveness of new biological drugs in the treatment of psoriasis Vulgaris of the trunk and extremities, in both palmoplantar phenotypes and in the lesions located predominantly on the scalp, these drugs usually have a slow and limited or null effect [3; 4]. The marked clinical differences and therapeutic response to the same treatments between these subgroups suggest that psoriasis should be considered as a spectrum of diseases rather than as a single entity [5]. Thus, it is important to unveil potential genetic factors that determine the location and phenotype of psoriasis lesions. Psoriasis is currently considered a systemic inflammatory disease with a multifactorial polygenic inheritance [6]. Genetic susceptibility is determined primarily by 65 loci known as psoriasis susceptibility regions (PSORS) that have been linked to psoriasis risk [7]. PSORS1, with the target allele HLA-C:06:02, contributes to 30-50% of genetic susceptibility, presenting its carriers with a 3-4 times higher risk of suffering from the disease [8]. In pustular forms, mutations and polymorphisms have been described in the genes CARD14, AP1S3, and IL36 RN [9; 10; 11], although the proportion of subjects harboring IL36 RN-mutated alleles seems to be higher in generalized pustular psoriasis (GPP) than in palmoplantar pustulosis (PPP), the prevalence of AP1S3 mutations seems to be similar across these disease types and CARD14 mutations are observed in only a small minority of cases [11; 12; 13]. However, not all patients carrying HLA-C:06:02 or the above-mentioned genes suffer from the disease [8]. This fact, together with the absence of total concordance between monozygotic twins, suggests that, although the influence of these genetic factors in psoriasis is evident, there must be other genetic or epigenetic determinants of the disease and its phenotypic variants. Each autosomal gene has two different copies originating from each parent. However, certain DNA regions have Copy Number Variations (CNVs) caused by duplications or deletions that result in a higher or lower number of copies [14; 15].