title: The OTF3 gene polymorphism confers susceptibility to psoriasis independent of the association of HLA-Cw*0602.
abstract: Psoriasis has been strongly associated to HLA-Cw6, but it remains unclear whether 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 disease susceptibility or whether it acts only as a marker for the susceptibility allele. We examined a sample of 95 type I psoriasis patients and 104 Spanish 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 samples were genotyped by polymerase chain reaction/sequence-specific primers (HLA-C), polymerase chain reaction/sequence-specific primers (HLA-B), radioactive polymerase chain reaction (MICA-TM polymorphism in the transmembrane region), and polymerase chain reaction/restriction fragment length polymorphism (protein S and octamer transcription factor-3). Our results show a significant increase of Cw*0602 in psoriasis patients (odds ratio = 3.64; pc < 0.0006). A significant association between the beta allele of octamer transcription factor-3 (HindIII) and psoriasis was also detected (odds ratio = 3.76; pc < 0.0003). The allele octamer transcription factor-3B (etiologic fraction = 0.62) was found to be more strongly associated to psoriasis vulgaris than Cw*0602 (etiologic fraction = 0.35) and the increase of octamer transcription factor-3 B allele is independent of the linkage disequilibrium with Cw*0602 as this was also found in Cw*0602 negative patients (odds ratio = 3.63; pc < 0.015, etiologic fraction = 0.55). We did not detect an association between the corneodesmosin gene and psoriasis. This fact suggests that the psoriasis susceptibility gene is located within a critical region of 147 kb, telomeric to HLA-C and centromeric to the corneodesmosin gene, and the association of Cw6 to psoriasis may be secondary to linkage disequilibrium.
authors.affiliation: Department of Functional Biology, University of Oviedo, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Gonzalez
authors.forename: J
authors.initials: J
authors.lastname: Martinez-Borra
authors.forename: J S
authors.initials: JS
authors.lastname: Del Río
authors.forename: J
authors.initials: J
authors.lastname: Santos-Juanes
authors.forename: A
authors.initials: A
authors.lastname: Lopez-Vazquez
authors.forename: M
authors.initials: M
authors.lastname: Blanco-Gelaz
authors.forename: C
authors.initials: C
authors.lastname: López-Larrea
mesh_terms: D000293:Adolescent; D000328:Adult; D002503:Centromere / Q000737:chemistry / Q000276:immunology; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D050814:Octamer Transcription Factor-3; D011110:Polymorphism, Genetic; D011565:Psoriasis / Q000235:genetics*; D013030:Spain; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D015236:HLA-C Antigens; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D014157:Transcription Factors