Single-point haplotype scores telomeric to human leukocyte antigen-C give a high susceptibility major histocompatibility complex haplotype for psoriasis in a Caucasian population.

Psoriasis is a chronic inflammatory skin disease that affects 0.1%-5% depending on the population. PSORS1 is the major susceptibility locus, accounting for approximately 33%-50% of the genetic component of psoriasis among Caucasians. PSORS1 is located within the major histocompatibility complex (MHC) locus on 6p21.3. Its position has been refined to hundreds of kilobase and the region located at approximately 100-200 kb telomeric to human leukocyte antigen (HLA)-C is a very strong candidate. To determine the MHC psoriasis risk haplotype, we screened the whole 46 kb interval for single-nucleotide polymorphisms (SNP) and identified 138 SNP. We genotyped 29 SNP throughout this region in psoriatic nuclear families. We calculated the frequency of haplotypes generated by the 29 SNP using all genotyped founder individuals and found four common haplotype with frequency >0.10. We then used SNPtagger to derive the best six SNP and fed these into Transmit using 148 nuclear families. We found that CTGGAC haplotype is a single-point score haplotypes telomeric to HLA-C and gives a 1 df, chi2 of 50.27 (p<0.0001). Most importantly the six selected SNP accurately tagged the most common haplotype found in this region. Moreover, using the same program (Transmit) we show that the association with CTGGAC is higher than the one with HLA-Cw6 (chi2=10.53; p=0.0051). Our results give scores as high as the highest single-point scores suggesting that it is unlikely to be able to discriminate the origin of the association on this analysis on strength of association.

Genome-wide studies of psoriasis susceptibility loci: a review.

Psoriasis is a chronic inflammatory dermatosis affecting approximately 0.3-5% world-wide. Since 1997, nine genome-wide scans have been published in the search for predisposing genes to psoriasis and psoriatic arthritis. These genome-wide scans have provided results that both confirm earlier work, but which also suggest novel regions of interest on the genome. This article reviews the results of these genome-wide scans, in particular two novel regions on chromosomes 3p and 15p, and compares the study types and designs. The results in these two regions were compared in the different studies providing no further suggestive evidence, and we suggest that these results may be false-positives, population-specific susceptibility loci or due to the stratification used in the study design. We suggest stratifying the data into epidemiological subgroups in order to make the genome-wide scans more sensitive to loci specific to these subgroups. This approach could provide a much more powerful technique to study the genetics of a complex disease such as psoriasis.