Stronger association with HLA-Cw6 than with corneodesmosin (S-gene) polymorphisms in Swedish psoriasis patients

Psoriasis vulgaris is strongly associated with certain human leukocyte anti gens, especially in early onset. The purpose of this study was to study the HLA-Cw6 allele and its contribution to disease susceptibility in a set of 104 families with at least two affected siblings. A sequencing method was u tilized to examine the two exons that build up the antigen binding site of the C locus receptor. DNA from patients homozygous for Cw6 based on haploty pe information were sequenced. The results confirmed the identity of the Cw 6 allele in affected individuals with the consensus sequence for Cw*0602, W e screened the set of families for psoriasis patients homozygous for Cw6 an d found 11 individuals with a mean age at onset of 16.1 years. The correspo nding figure for the Cw6 heterozygotes was 18.45 years and for the Cw6-nega tives 22.36 years. This is indicative of a gene dose effect. We performed a transmission disequilibrium test (TDT) on the Cw6 allele per se, used as a biallelic marker. The analysis resulted in a P-value of 5.3 x 10(-17) (t16 7/nt45), This greatly exceeds our previous results of a TDT in the region, including microsatellite markers and single nucleotide polymorphisms (SNPs) in the coding part of the S gene (corneodesmosin), which is a suggested ca ndidate gene in the region. The maximum nonparametric linkage (NPL) value w as also reached using HLA-C as a marker. We conclude that Cw6 is the allele which shows the high- est degree of association with psoriasis in our set of families and we propose that it directly influences the age at onset of the disease rather than increasing the genetic load in accordance with a po lygenic theory.