Association Analysis Using Refined Microsatellite Markers Localizes a Susceptibility Locus for Psoriasis Vulgaris Within a 111 kb Segment Telomeric to the HLA-C Gene

Abstract

The HLA-Cw6 antigen has been associated with psoriasis vulgaris despite racial and ethnic differences. However, it remains unclear whether it is the HLA-Cw6 antigen itself or a closely linked, hitherto unidentified, locus that predisposes to the disease. Here, in order to map the susceptibility locus for psoriasis vulgaris precisely within the HLA class I region, 11 polymorphic microsatellite markers distributed throughout a 1060 kb segment surrounding the HLA-C locus were subjected to association analysis in Japanese psoriasis vulgaris patients. Statistical analyses of the distribution and deviation from Hardy-Weinberg equilibrium of the allelic frequency at each micro-satellite locus revealed that the pathogenic gene for psoriasis vulgaris is located within a reduced interval of 111 kb spanning 89-200 kb telomeric of the HLA-C gene. In addition to three known genes, POU5F1, TCF19 and S, this 111 kb fragment contains four new, expressed genes identified in the course of our genomic sequencing of the entire HLA class I region. Therefore, these seven genes are the potential candidates for susceptibility to psoriasis vulgaris.

Possible relations between the polymorphisms of the cytokines IL-19, IL-20 and IL-24 and plaque-type psoriasis

“…4,5 The susceptibility region in chromosome 6 (PSORS1-psoriasis susceptibility 1) has refined to an approximately B300 kb region around HLA-C gene and contains several candidate genes including HLA-C, octamer transcription factor-3 (OTF3), transcription factor-19 (TCF19), corneodesmosin (CDSN) and a-helix coiled-coil rod homolog (HCR) genes. [6][7][8][9] In addition, several non-MHC psoriasis susceptibility loci (1q21, 16q and 17q) associate with different AIDs such as systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and diabetes. 10 This provides support for the hypothesis that susceptibility to different AIDs may be driven by the same susceptibility genes and immunopathways.…”

Corneodesmosin Expression in Psoriasis Vulgaris Differs from Normal Skin and Other Inflammatory Skin Disorders

“…In addition to increasing genetic evidence (Nair et al, 2000;Oka et al, 1999) against HLA-C as a susceptibility gene for psoriasis, the biological characteristics of HLA-C do not support a functional role in psoriasis. However, the major histocompatibility complex contains many non-HLA genes and HLA-C may simply be acting as a genetic marker for the psoriasissusceptibility gene(s) in close linkage disequilibrium with HLA-C. One such gene is the Cdsn gene, which, because of its genomic position and biological function, is a good potential candidate for psoriasis susceptibility.…”

“…Multiple studies indicate genetic linkage of psoriasis to a locus on chromosome 6p21.3 (PSORS1), accounting for 35% to 50% of the genetic contribution to psoriasis (Burden et al, 1998;Nair et al, 1997;Trembath et al, 1997). Linkage disequilibrium mapping studies have refined the PSORS1 locus to an approximately 300 kb region of chromosome 6p21.3 (Balendran et al, 1999;Nair et al, 2000;Oka et al, 1999), which contains the genes for HLA-C and Cdsn (160 kb telomeric of HLA-C) (Zhou and Chaplin, 1993).…”

Steroidogenic Acute Regulatory Protein-binding Protein Cloned by a Yeast Two-hybrid System

“…The first translation start site ATG in clone 4 is present in exon 4 in SBP in the testis. Clone 4 encodes an N-terminally truncated 656-amino acid region of the HCR protein (757 amino acids) (28) (Fig. 5C).…”