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.

Conserved extended haplotypes of the major histocompatibility complex: further characterization

“…Although such an interpretation may be the correct one at times, many other MHC genes deserve attention as alternative explanations for HLA associations. Some investigators have considered these non-HLA genes [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and these efforts would be facilitated by better characterization of the relationships among these MHC genes.…”

The genetic polymorphisms of POU5F1 gene are associated with psoriasis vulgaris in Chinese

“…Since the penetrance of HLA-Cw*0602 is only about 10%, it has been proposed that other genomic segments near the HLA-C locus might be also involved in determining PV susceptibility [3]. POU5F1 gene, located 96 kb telomeric to the HLA-C locus, is considered a possible psoriasis candidate gene because of its location within the PSORS1 locus [4,5]. POU5F1 is a sequence-specific transcription factor essential for keeping embryonic stem cells in a pluripotent status [6], and the activation of POU5F1 results in dysplastic growths in epithelial tissues [7].…”

“…The POU5F1 gene has been noted as being expressed in embryonic stem cells and tumor cells but not in differentiated tissues. Previous studies have shown that the POU5F1 +1377T (formerly called OTF3-B) allele is strongly associated with psoriasis in the Caucasian population [4,5]. However, until now, no comprehensive study of all exonic single nucleotide polymorphisms (SNPs) of POU5F1 gene has been documented in Chinese patients with PV.…”

HLA-Cw*0602 Associates More Strongly to Psoriasis in the Swedish Population than Variants of the Novel 6p21.3 Gene PSORS1C3

“…However, except in some isolated studies none of these candidates have associated more strongly than HLACw*0602 across diverse populations (13)(14)(15)(16)(17)(18)(19)(20). Therefore we have continued the screening for new candidates in the area between HLA-C and P0U5F1.…”