Cytotoxic T lymphocyte-associated antigen 4 gene polymorphisms associated with psoriasis vulgaris in a Caucasian population

Psoriasis vulgaris is an inflammatory skin disease that is inherited as a complex trait. Increased levels of inflammatory cytokines and the abundance of activated T-cells and antigen-presenting cells in lesional psoriatic epidermis suggest that activated T-cells play an important role in triggering and perpetuating the disease. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) mediates inhibition of T-cell activation by B7 surface protein binding. Mutations in the CTLA-4 gene, including those in untranslated regions that regulate messenger expression, may produce qualitative or quantitative alterations in B7 surface protein binding that lead to T-cell activation and an increased expression of inflammatory cytokines. To investigate the possibility of CTLA-4 involvement in psoriasis, 83 patients with psoriasis and 291 controls were genotyped for the Thr17Ala polymorphism at exon 1 of the CTLA-4 gene. The Thr allele was found significantly more often in patients (OR= 2.0, 95% CI=1.2-3.3, P=0.0037) and with more homozygotes (76% vs. 56%) and less heterozygotes (22% vs. 40%) than in controls (P<0.006). Moreover, the dinucleotide repeat polymorphism (CTLA-4[AT]n) in the 3'UTR region of the gene was analyzed in 83 patients and 102 controls. Results showed that the 130bp allele was positively associated to psoriasis (OR= 3.8, 95%CI= 1.6-9.4, Pc(18)=0.038). Estimates of haplotypc frequencies of the two polymorphic loci yielded the highest psoriasis risk for the two associated alleles (OR=6.0 95%CI=2-17.9. Pc(36) = 0.014). Our findings provide an explanation at genetic level for some of the histological and immunological aspects of the disease. © 2001 Blackwell Science Ltd.