| Title: | Differences in Clinical Features and Comorbid Burden between HLA-C ∗06:02 Carrier Groups in >9,000 People with Psoriasis |
| Journal: | Journal of Investigative Dermatology |
| Published: | 10 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34767815/ |
| DOI: | https://doi.org/10.1016/j.jid.2021.08.446 |
| URL: | https://kclpure.kcl.ac.uk/portal/en/publications/1c4119d5-f34a-42a0-a661-fc884f50bbea |
| Citations: | 14 (12 in last 2 years) as of 8 Aug 2024 |
Publication 4692
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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.</p>
8 Keywords
- Alleles
- Biomarkers
- Cross-Sectional Studies
- Female
- Genetic Predisposition to Disease
- HLA-C Antigens
- Humans
- Psoriasis
115 Authors
- 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
- Anthony Bewley
- 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
- Ruth Murphy
- Paul Norris
- Caroline Owen
- 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
- Andrew Wright
Enabling scientific discoveries that improve human health