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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.
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
Volume: 142
Issue: 6
Pages: 1617-1628.e10
Print publication date: 01/06/2022
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.
URL: https://doi.org/10.1016/j.jid.2021.08.446
DOI: 10.1016/j.jid.2021.08.446
PubMed id: 34767815
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