Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6%, χ² = 14.65, p = 0.000129). This frequency rose to 39.5% in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α₁-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5% of the cases against the 50.82% of controls (χ² = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15% of patients and in 0% of controls (χ² = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future.

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