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

Lookup NU author(s): Dr Konstantinos Douroudis, Professor Nick ReynoldsORCiD, Dr Shyamal Wahie



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2021 The Authors. 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.

Publication metadata

Author(s): Douroudis K, Ramessur R, Barbosa IA, Baudry D, Duckworth M, Angit C, Capon F, Chung R, Curtis CJ, Di Meglio P, Goulding JMR, Griffiths CEM, Lee SH, Mahil SK, Parslew R, Reynolds NJ, Shipman AR, Warren RB, Yiu ZZN, Simpson MA, Barker JN, Dand N, Smith CH, Evans I, Murphy R, McPherson T, Kleyn E, Laws P, Becher G, Bewley A, Rashid A, Alabas O, Morrison S, Ahmed S, Pearson E, Richards J, Mackenzie T, Kirby B, Burden D, Lawson L, McElhone K, Ormerod A, Owen C, Aldoori N, Ali M, Anstey A, Antony F, Archer C, August S, Balasubramaniam P, Baxter K, Bonsall A, Brown V, Burova K, Butt A, Caswell M, Cliff S, Costache M, Darne S, Davies E, DeGiovanni C, Desai T, DeSilva B, Diba V, Domanne E, Dymond H, Fahy C, Ferguson L, Gkini M-A, Godwin A, Hammonds F, Johnson S, Joseph T, Kalavala M, Khorshid M, Labinoti L, Lawson N, Layton A, Lees T, Levell N, Lewis H, Lyon C, McBride S, McCormack S, McKenna K, Mellor S, Norris P, Popli U, Perera G, Ponnambath N, Ramsay H, Ranasinghe A, Reeken S, Rose R, Rotarescu R, Salvary I, Sands K, Sinha T, Stefanescu S, Sundararaj K, Taghipour K, Taylor M, Thomson M, Topliffe J, Verdolini R, Wachsmuth R, Wade M, Wahie S, Walsh S, Walton S, Wilcox L, Wright A

Publication type: Article

Publication status: Published

Journal: Journal of Investigative Dermatology

Year: 2022

Pages: E-Pub ahead of Print

Online publication date: 10/11/2021

Acceptance date: 30/08/2021

Date deposited: 08/02/2022

ISSN (print): 0022-202X

ISSN (electronic): 1523-1747

Publisher: Elsevier B.V.


DOI: 10.1016/j.jid.2021.08.446

PubMed id: 34767815


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Funder referenceFunder name
821511 (Biomarkers in Atopic Dermatitis and Psoriasis)
Guy’s and St Thomas’s Charity (grant reference STR130505)
Maudsley Charity (grant reference 980)
RG2/10: RG2/10