ERAP1 and HLA-C*06 are strongly associated with the risk of psoriasis in the population of northern Poland

Introduction: HLA-C*06 is a major psoriasis genetic risk marker. Recent reports have been focused on the role of different polymorphisms within genes involved in the functioning of the epidermal barrier and antigen processing in the pathogenesis of psoriasis. Data on the association between genetic variants of LCE3B_LCE3C, CSTA, ERAP1, ZAP70 and this dermatosis in the population from Eastern Europe are lacking. Aim: To compare the association between known genetic risk markers and psoriasis in a cohort of northern Polish patients with psoriasis and healthy controls. Material and methods: Based on previous studies’ results, five susceptibility loci: HLA-C, LCE3C_LCE3B, ERAP1, ZAP70 and CSTA were selected for genotyping in 148 patients with chronic plaque psoriasis and 146 healthy controls. Each patient with this disease was clinically assessed with the Psoriasis Area and Severity Index. Results: The study population showed a significant association of psoriasis and a single nucleotide polymorphism in the ERAP1 – rs26653 (p = 3.11 × 10–5) and HLA-C*06 allele (p = 1.02 × 10–11) when compared with the control group. The presence of HLA-C*06 or rs26653 G allele significantly increased the risk of psoriasis by 2.4 times or twice, respectively. Carrying rs26653 C allele considerably decreased the risk of psoriasis by 1.5 times. Conclusions: In the context of pathogenesis of psoriasis, our findings might give the evidence on disturbances in the proteolytic processing of N-terminal fragments of antigens presented via major histocompatibility complex class I to T cells

Evaluation of Psoriasis Genetic Risk Based on Five Susceptibility Markers in a Population from Northern Poland

<div><p>Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (<i>HLA-C</i>, <i>ERAP1</i>, <i>ZAP70</i>) and in the skin barrier function (<i>LCE3</i>, <i>CSTA</i>) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8×10⁻⁷). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9×10⁻¹⁴). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative <i>HLA-C*06</i> allele.</p></div

The odds ratios for each of the analyzed psoriasis genetic markers in the case-control samples from northern Poland.

<p>The odds ratios for each of the analyzed psoriasis genetic markers in the case-control samples from northern Poland.</p

Comparison of ROC curves for prediction of psoriasis with the use of five psoriasis susceptibility markers analyzed separately and for cGRS and wGRS values obtained for these markers.

<p>Comparison of ROC curves for prediction of psoriasis with the use of five psoriasis susceptibility markers analyzed separately and for cGRS and wGRS values obtained for these markers.</p

The review of SNPs of <i>CSTA</i>, <i>ERAP1</i> and <i>ZAP70</i> genes, which were tested for correlation with the risk of psoriasis.

<p>The review of SNPs of <i>CSTA</i>, <i>ERAP1</i> and <i>ZAP70</i> genes, which were tested for correlation with the risk of psoriasis.</p

Cohort characteristics.

<p>Cohort characteristics.</p

Comparison of cGRS and wGRS values for the tested panel of five susceptibility markers between patients with psoriasis and healthy controls.

<p>Comparison of cGRS and wGRS values for the tested panel of five susceptibility markers between patients with psoriasis and healthy controls.</p