# Soriasis and Seasonality: Exploring the Genetic and Epigenetic Interactions
## 3 Molecular Background of Psoriasis
### Epigenetics of Psoriasis
#### 3.2.1 DNA Methylation  
_OAS2_ (2'-5'-oligoadenylate synthetase 2) gene is an antiviral enzyme activated by innate immune system, and its overexpression has been reported in patients with inflammatory diseases. A study by [PERSON] et al. [48] revealed that the _OAS2_ gene was hypomethyllated in PsV skin samples from 39 psoriatic patients. In another study by [PERSON] et al. [49], over 1300 gene transcripts were altered in 20 skin samples of the patients with PsV (12 biopsies of skin affected with psoriasis and 8 biopsies of uninvolved skin) compared to 10 samples from healthy volunteers. Out of 1108 different genes' expressions, 674 genes' CpG sites were hypermethylated and 444 hypomethyllated. The altered CpG site methylation was observed and associated with transcriptional upregulation of genes such as _KYNUI_, _OAS2_, _S100A12_, and _SERPINB3_, which are associated with PsV. The authors also reported that after one month of therapy with TNF-\(\alpha\) inhibitors in psoriatic patients, the methylation reversed toward the non-posoriatic state observed in healthy subjects. [PERSON] et al. [50] performed genome-wide analysis using epidermal samples to investigate global DNA methylation in patients with psoriasis. Authors mapped over thirty-five thousand differently methylated sites in patients with PsV compared to healthy volunteers. Additionally, a large number of differently methylated sites were present in clinically uninvolved skin samples versus healthy epidermis, suggesting the presence of a pre-lesion state in clinically healthy skin  
\begin{table}
\begin{tabular}{c c c} \hline
**Described** & **References** & **Clinical Features/Implications** \\
**Polymorphism** & & \\ \hline _HLA-B\({}^{*}\)27_ & & \\ _HLA-B\({}^{*}\)39_ & & [26; 42; 43; 44] & Higher risk of PsA development. \\ _HLA-B\({}^{*}\)38_ & & \\ _HLA-B\({}^{*}\)08_ & & \\ \hline _HLA-B\({}^{*}\)08_ & [26; 44] & Asymmetric sacroliiitis, peripheral arthritis ankylosis, and increased joint damage. \\ \hline _HLA-B\({}^{*}\)27_ & [26; 44] & Symmetric sacroliiitis, dactylitis, and enthesitis development. \\ \hline _HLA-C\({}^{*}\)06:02_ & [28; 45] & An earlier onset of PsV and a later onset of PsA. \\  & & Photosensitive psoriasis. \\ \hline _CARD14_ & [19; 31; 32; 33] & Psoriasis and/or features of PRP and GPP. \\  & & Photosensitive psoriasis. \\ \hline _FTO_ & & \\ _CALCR_ & [41; 46] & PsV associated with obesity. \\ _AC003006.7_ & & \\ \hline \end{tabular} Abbreviations: PsA— psoriatic arthritis; PsV— psoriasis vulgaris; PRP—pityriasis rubra pilaris; GPP—generalized pustular psoriasis.  
\end{table}
Table 1: Examples of gene polymorphisms associated with psoriasis and their clinical implications.  
with no psoriatic symptoms. [PERSON] et al. [51] profiled the methylation of psoriatic lesions and adjacent normal skin tissues of 24 patients with PsV (48 pairs) and compared to a cohort of 30 skin samples of 15 healthy participants. Genome-wide methylation profiling revealed an inverse correlation between methylation and overlapping gene activity located in _PSOR_ regions, including _100A9_, _SELENBP1_, _CARD14_, _KAZN_, and _PTPN_.