1. ¹Department of Dermatology, University of Michigan, Ann Arbor, Michigan, USA
2. ²deCODE Genetics, Reykjavik, Iceland
3. ³Department of Immunology, National University Hospital of Iceland, Reykjavik, Iceland

Correspondence: Professor Johann E. Gudjonsson, Department of Dermatology, University of Michigan, 1910 Taubman Center, Ann Arbor, Michigan 48109, USA. E-mail: johanng@med.umich.edu

Received 23 January 2005; Revised 18 September 2005; Accepted 10 November 2005; Published online 26 January 2006.

Abstract

A major susceptibility gene for psoriasis is located in the major histocompatibility complex class I region on chromosome 6 very close to the HLA-Cw6 gene. We collected a cohort of 1,019 patients with chronic plaque psoriasis. The patients were typed for HLA-C and HLA-B. A total of 654 (64.2%) were HLA-Cw^*0602 positive but 365 (35.8%) carried other HLA-C alleles. We confirmed that HLA-Cw^*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10^-10), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03). A striking new finding was a diverging pattern of disease severity in HLA-Cw^*0602 positive and negative patients depending on the age of onset of the disease (P=0.0006). HLA-Cw^*0602 positive women also had more frequent remissions during pregnancy (P<0.0001). All types of nail changes were, however, more common in the Cw^*0602 negative patients (P=0.003) and they more often had multiple types of nail lesions (P<0.0001). The three ancestral haplotypes of Cw^*0602 all conferred an increase in odds ratio but showed no difference in any of the clinical features studied. Our findings indicate that the genetic factor on chromosome 6 has a strong influence on the phenotype of the disease, and underline that differences in clinical features of psoriasis may be to a large extent genetically determined.