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DIFFERENCES IN CLINICAL FEATURES AND COMORBID BURDEN BETWEEN HLA-C*06:02CARRIER GROUPS IN MORE THAN 9,000 PEOPLE WITH PSORIASIS

DIFFERENCES IN CLINICAL FEATURES AND COMORBID BURDEN BETWEEN HLA-C*06:02CARRIER GROUPS IN MORE THAN 9,000 PEOPLE WITH PSORIASIS

Authors :
Douroudis, Konstantinos
Ramessur, Ravi
Barbosa, Ines A.
Baudry, David
Duckworth, Michael
Angit, Caroline
Capon, Francesca
Chung, Raymond
Curtis, Charles J.
Di Meglio, Paola
Goulding, Jonathan MR.
Griffiths, Christopher EM.
Lee, Sang Hyuck
Mahil, Satveer K.
Parslew, Richard
Reynolds, Nick J.
Shipman, Alexa R.
Warren, Richard B.
Yiu, Zenas ZN.
Simpson, Michael A.
Barker, Jonathan N.
Dand, Nick
Smith, Catherine H.
Source :
Journal of Investigative Dermatology; 20210101, Issue: Preprints
Publication Year :
2021

Abstract

The identification of robust endotypes – disease subgroups of clinical relevance – is fundamental to stratified medicine. We hypothesised that HLA-C*06:02status, the major genetic determinant of psoriasis, defines a psoriasis endotype of clinical relevance. Using two UK-based cross-sectional datasets – an observational severe psoriasis study (Biomarkers of Systemic Treatment Outcomes in Psoriasis, BSTOP; 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*06:02allele) compared to 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 (BSTOP: 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, odds ratio [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 (BSTOP: waist circumference difference 2.0 cm, p=8.4×10-4; UK Biobank: 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 multi-marker stratified medicine approaches.

Details

Language :
English
ISSN :
0022202X and 15231747
Issue :
Preprints
Database :
Supplemental Index
Journal :
Journal of Investigative Dermatology
Publication Type :
Periodical
Accession number :
ejs58225320
Full Text :
https://doi.org/10.1016/j.jid.2021.08.446