Is the TAP2 single nucleotide polymorphism rs241447 truly associated with psoriasis in Poles

Abstract Psoriasis vulgaris (PsV) is strongly associated with HLA-C*06:02. HLA class I molecules present antigenic peptides to CD8+ T lymphocytes. Peptide transport from cytosol to the endoplasmic reticulum is mediated by a transporter associated with antigen processing (TAP) composed of TAP1 and TAP2 polymorphic proteins. Here, we compared the distribution of three coding single nucleotide polymorphisms (SNPs), rs1057141 in TAP1 and rs1800454 and rs241447 in TAP2 as well as the HLA-C*06:02 allele in 438 patients diagnosed with PsV and 493 control individuals. In patients and controls non-stratified by HLA-C*06:02, TAP2 rs241447 was associated with PsV but other TAP1 and TAP2 SNPs were not. By contrast, stratification according to the Svejgaard and Ryder formula, as well as a logistic regression approach and haplotype analysis demonstrated that the effect of TAP2 rs241447 was entirely related to the presence of HLA-C*06:02. The secondary effect of TAP2 rs241447 in relation to primary effect of HLA-C*06:02 resulted from linkage disequilibrium (albeit not strong) between both markers. We conclude that joint coexistence of HLA-C*06:02 and the TAP2 rs241447C risk allele on the extended haplotype might explain the effect of TAP2 observed by us.