The OTF3 gene polymorphism confers susceptibility to psoriasis independentof the association of HLA-Cw*0602

Psoriasis has been strongly associated to HLA-Cw6, but it remains unclear w hether Cw6 itself or a closely linked gene is associated with the disease. The aim of this study was to clarify whether the HLA-C itself determines di sease susceptibility or whether it acts only as a marker for the susceptibi lity allele. We examined a sample of 95 type I psoriasis patients and 104 S panish matched controls to investigate whether HLA-Cw*0602 or other closely related class I loci, such as HLA-B and MICA (which are centromeric to HLA -C), or corneodesmosin gene and octamer transcription factor-3 genes (which are telomeric to HLA-C), might play a part in disease development. DNA sam ples were genotyped by polymerase chain reaction/sequence-specific primers (HLA-C), polymerase chain reaction/sequence-specific primers (HLA-B), radio active polymerase chain reaction (MICA-TM polymorphism in the transmembrane region), and polymerase chain reaction/restriction fragment length polymor phism (protein S and octamer transcription factor-3). Our results show a si gnificant increase of Cw*0602 in psoriasis patients (odds ratio = 3.64; p(c ) < 0.0006). A significant association between the beta allele of octamer t ranscription factor-3 (HindIII) and psoriasis was also detected (odds ratio = 3.76; p(c) < 0.0003). The allele octamer transcription factor-3B (etiolo gic fraction = 0.62) was found to be more strongly associated to psoriasis vulgaris than Cw*0602 (etiologic fraction = 0.35) and the increase of octam er transcription factor-3 B allele is independent of the linkage disequilib rium with Cw*0602 as this was also found in Cw*0602 negative patients (odds ratio = 3.63; p(c) < 0.015, etiologic fraction = 0.55). We did not detect an association between the corneodesmosin gene and psoriasis. This fact sug gests that the psoriasis susceptibility gene is located within a critical r egion of 147 kb, telomeric to HLA-C and centromeric to the corneodesmosin g ene, and the association of Cw6 to psoriasis may be secondary to linkage di sequilibrium.