1. Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis
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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. Simpson, Jonathan N. Barker, Nick Dand, Catherine H. Smith, Ian Evans, Ruth Murphy, Tess McPherson, Elise Kleyn, Philip Laws, Gabrielle Becher, Anthony Bewley, Amir Rashid, Oras Alabas, Simon Morrison, Shehnaz Ahmed, Eleanor Pearson, Josh Richards, Teena Mackenzie, Brian Kirby, David Burden, Linda Lawson, Kathleen McElhone, Anthony Ormerod, Caroline Owen, Nadia Aldoori, Mahmud Ali, Alex Anstey, Fiona Antony, Charles Archer, Suzanna August, Periasamy Balasubramaniam, Kay Baxter, Alexandra Bonsall, Victoria Brown, Katya Burova, Aamir Butt, Mel Caswell, Sandeep Cliff, Mihaela Costache, Sharmela Darne, Emily Davies, Claudia DeGiovanni, Trupti Desai, Bernadette DeSilva, Victoria Diba, Eva Domanne, Harvey Dymond, Caoimhe Fahy, Leila Ferguson, Maria-Angeliki Gkini, Alison Godwin, Fiona Hammonds, Sarah Johnson, Teresa Joseph, Manju Kalavala, Mohsen Khorshid, Liberta Labinoti, Nicole Lawson, Alison Layton, Tara Lees, Nick Levell, Helen Lewis, Calum Lyon, Sandy McBride, Sally McCormack, Kevin McKenna, Serap Mellor, Paul Norris, Urvi Popli, Gay Perera, Nabil Ponnambath, Helen Ramsay, Aruni Ranasinghe, Saskia Reeken, Rebecca Rose, Rada Rotarescu, Ingrid Salvary, Kathy Sands, Tapati Sinha, Simina Stefanescu, Kavitha Sundararaj, Kathy Taghipour, Michelle Taylor, Michelle Thomson, Joanne Topliffe, Roberto Verdolini, Rachel Wachsmuth, Martin Wade, Shyamal Wahie, Sarah Walsh, Shernaz Walton, Louise Wilcox, and Andrew Wright
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medicine.medical_specialty ,Endotype ,HLA-C Antigens ,Dermatology ,Disease ,Biochemistry ,Psoriatic arthritis ,Internal medicine ,Psoriasis ,medicine ,Humans ,Genetic Predisposition to Disease ,Clinical significance ,Expressivity (genetics) ,Molecular Biology ,Alleles ,business.industry ,Cell Biology ,Odds ratio ,medicine.disease ,Biobank ,Cross-Sectional Studies ,Female ,business ,Biomarkers - Abstract
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.
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