Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis

Konstantinos Douroudis, Ravi Ramessur, Ines A. Barbosa, David Baudry, Michael Duckworth, Caroline Angit, Francesca Capon, Raymond Chung, Charles J. Curtis, Paola Di Meglio, Jonathan M.R. Goulding, Christopher E.M. Griffiths, Sang Hyuck Lee, Satveer K. Mahil, Richard Parslew, Nick J. Reynolds, Alexa R. Shipman, Richard B. Warren, Zenas Z.N. Yiu, Michael A. SimpsonJonathan N. Barker, Nick Dand, Catherine H. Smith*, BADBIR, BSTOP Study Groups

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


The identification of robust endotypes—disease subgroups of clinical relevance—is fundamental to stratified medicine. We hypothesized that HLA-C∗06:02 status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two United Kingdom–based cross-sectional datasets—an observational severe-psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis; n = 3,767) and a large population-based bioresource (UK Biobank, including n = 5,519 individuals with psoriasis)—we compared demographic, environmental, and clinical variables of interest in HLA-C∗06:02–positive (one or two copies of the HLA-C∗06:02 allele) with those in HLA-C∗06:02‒negative (no copies) individuals of European ancestry. We used multivariable regression analyses to account for mediation effects established a priori. We confirm previous observations that HLA-C∗06:02–positive status is associated with earlier age of psoriasis onset and extend findings to reveal an association with disease expressivity in females (Biomarkers of Systemic Treatment Outcomes in Psoriasis: P = 2.7 × 10–14, UK Biobank: P = 1.0 × 10–8). We also show HLA-C∗06:02–negative status to be associated with characteristic clinical features (large plaque disease, OR for HLA-C∗06:02 = 0.73, P = 7.4 × 10–4; nail involvement, OR = 0.70, P = 2.4 × 10–6); higher central adiposity (Biomarkers of Systemic Treatment Outcomes in Psoriasis: waist circumference difference of 2.0 cm, P = 8.4 × 10–4; UK Biobank: waist circumference difference of 1.4 cm, P = 1.5 × 10–4), especially in women; and a higher prevalence of other cardiometabolic comorbidities. These findings extend the clinical phenotype delineated by HLA-C∗06:02 and highlight its potential as an important biomarker to consider in future multimarker stratified medicine approaches.

Original languageEnglish
Pages (from-to)1617-1628.e10
JournalJournal of Investigative Dermatology
Issue number6
Publication statusPublished - Jun 2022
Externally publishedYes


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