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

Konstantinos Douroudis; Ravi Ramessur; Ines Biscaia De Andrade Barbosa; David Baudry; Michael Duckworth; Caroline Angit; Francesca Capon; Raymond Chung; Charles Curtis; Paola DiMeglio; Jonathan Goudling; Christopher Griffiths; Sang Lee; Satveer Mahil; Richard Parslew; Nick Reynolds; Alexa Shipman; richard warren; Zenas Yiu; Michael Simpson; Jonathan Barker; Nick Dand; Catherine Smith

doi:doi: 10.1016/j.jid.2021.08.446

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

Konstantinos Douroudis, Ravi Ramessur, Ines Biscaia De Andrade Barbosa, David Baudry, Michael Duckworth, Caroline Angit, Francesca Capon, Raymond Chung, Charles Curtis, Paola DiMeglio, Jonathan Goudling, Christopher Griffiths, Sang Lee, Satveer Mahil, Richard Parslew, Nick Reynolds, Alexa Shipman, richard warren, Zenas Yiu, Michael SimpsonJonathan Barker, Nick Dand, Catherine Smith^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The identification of robust endotypes – disease subgroups of clinical relevance – is fundamental to stratified medicine. We hypothesised that HLA-C*06:02 status, 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*06:02 allele) 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.

Original language	English
Journal	Journal of Investigative Dermatology
DOIs	https://doi.org/doi: 10.1016/j.jid.2021.08.446
Publication status	Published - 21 Nov 2021

Keywords

PSORIASIS
HLA-C Antigens/genetics
Stratified medicine

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doi: 10.1016/j.jid.2021.08.446

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Differences in Clinical Features and Comorbid Burden between HLA-C0602 carrier groupsFinal published version, 605 KBLicence: CC BY-NC-ND

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Douroudis, K., Ramessur, R., Biscaia De Andrade Barbosa, I., Baudry, D., Duckworth, M., Angit, C., Capon, F., Chung, R., Curtis, C., DiMeglio, P., Goudling, J., Griffiths, C., Lee, S., Mahil, S., Parslew, R., Reynolds, N., Shipman, A., warren, R., Yiu, Z., ... Smith, C. (2021). DIFFERENCES IN CLINICAL FEATURES AND COMORBID BURDEN BETWEEN HLA-C*06:02 CARRIER GROUPS IN MORE THAN 9,000 PEOPLE WITH PSORIASIS. Journal of Investigative Dermatology. https://doi.org/doi: 10.1016/j.jid.2021.08.446

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

abstract = "The identification of robust endotypes – disease subgroups of clinical relevance – is fundamental to stratified medicine. We hypothesised that HLA-C*06:02 status, 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*06:02 allele) 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. ",

keywords = "PSORIASIS, HLA-C Antigens/genetics, Stratified medicine",

author = "Konstantinos Douroudis and Ravi Ramessur and {Biscaia De Andrade Barbosa}, Ines and David Baudry and Michael Duckworth and Caroline Angit and Francesca Capon and Raymond Chung and Charles Curtis and Paola DiMeglio and Jonathan Goudling and Christopher Griffiths and Sang Lee and Satveer Mahil and Richard Parslew and Nick Reynolds and Alexa Shipman and richard warren and Zenas Yiu and Michael Simpson and Jonathan Barker and Nick Dand and Catherine Smith",

year = "2021",

month = nov,

day = "21",

doi = "doi: 10.1016/j.jid.2021.08.446",

language = "English",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "Nature Publishing Group",

}

Douroudis, K , Ramessur, R, Biscaia De Andrade Barbosa, I, Baudry, D, Duckworth, M, Angit, C, Capon, F , Chung, R , Curtis, C, DiMeglio, P, Goudling, J, Griffiths, C, Lee, S , Mahil, S, Parslew, R, Reynolds, N, Shipman, A, warren, R, Yiu, Z, Simpson, M , Barker, J , Dand, N & Smith, C 2021, 'DIFFERENCES IN CLINICAL FEATURES AND COMORBID BURDEN BETWEEN HLA-C*06:02 CARRIER GROUPS IN MORE THAN 9,000 PEOPLE WITH PSORIASIS', Journal of Investigative Dermatology. https://doi.org/doi: 10.1016/j.jid.2021.08.446

TY - JOUR

T1 - DIFFERENCES IN CLINICAL FEATURES AND COMORBID BURDEN BETWEEN HLA-C*06:02 CARRIER GROUPS IN MORE THAN 9,000 PEOPLE WITH PSORIASIS

AU - Douroudis, Konstantinos

AU - Ramessur, Ravi

AU - Biscaia De Andrade Barbosa, Ines

AU - Baudry, David

AU - Duckworth, Michael

AU - Angit, Caroline

AU - Capon, Francesca

AU - Chung, Raymond

AU - Curtis, Charles

AU - DiMeglio, Paola

AU - Goudling, Jonathan

AU - Griffiths, Christopher

AU - Lee, Sang

AU - Mahil, Satveer

AU - Parslew, Richard

AU - Reynolds, Nick

AU - Shipman, Alexa

AU - warren, richard

AU - Yiu, Zenas

AU - Simpson, Michael

AU - Barker, Jonathan

AU - Dand, Nick

AU - Smith, Catherine

PY - 2021/11/21

Y1 - 2021/11/21

N2 - The identification of robust endotypes – disease subgroups of clinical relevance – is fundamental to stratified medicine. We hypothesised that HLA-C*06:02 status, 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*06:02 allele) 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.

AB - The identification of robust endotypes – disease subgroups of clinical relevance – is fundamental to stratified medicine. We hypothesised that HLA-C*06:02 status, 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*06:02 allele) 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.

KW - PSORIASIS

KW - HLA-C Antigens/genetics

KW - Stratified medicine

U2 - doi: 10.1016/j.jid.2021.08.446

DO - doi: 10.1016/j.jid.2021.08.446

M3 - Article

SN - 0022-202X

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

ER -

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

Abstract

Keywords

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