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An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts

Lookup NU author(s): Dr Laura Lane, Professor Heather Cordell, Professor Simon Pearce, Dr Timothy Cheetham, Dr Anna Mitchell

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.CONTEXT: The genetic background of young-onset Graves disease (GD) remains largely unknown. An intronic variant in human leukocyte antigen (HLA) complex P5 (HCP5) has previously been associated with GD susceptibility and age of onset in a cohort of Polish patients. OBJECTIVE: We aimed to investigate the association of the HCP5 variant rs3094228 with GD susceptibility and age of onset in a UK cohort and conduct a meta-analysis of UK and Polish data. DESIGN AND PARTICIPANTS: rs3094228 was genotyped in 469 UK patients with GD using Taqman chemistry. Genotype frequencies were compared with genotypic data available from the Wellcome Trust case-control consortium using logistic regression analysis. To determine whether rs3094228 is independently associated with age of GD onset, the HLA DRB1*0301 tagging variant, rs535777, was also genotyped. RESULTS: The C allele of rs3094228 was overrepresented in the UK GD cohort compared with controls (P allele=5.08 × 10-9, odds ratio 1.76; [95% confidence interval, 1.46-2.13]). This association was more marked in young-onset GD (<30 years) (P allele=1.70 × 10-10 vs P allele=0.0008). The meta-analysis of UK and Polish data supported the association of the C allele with GD susceptibility (P allele=1.79 × 10-5) and age of onset (P allele=5.63 × 10-8). Haplotype analysis demonstrated that rs3094228 is associated with age of GD onset (P = 2.39 × 10-6) independent of linkage disequilibrium with HLA DRB1*0301. CONCLUSION: The rs3094228 HCP5 polymorphism is independently associated with GD susceptibility and age of onset in a UK GD cohort. Our findings indicate a potential role of long noncoding ribonucleic acids, including HCP5, in GD pathogenesis, particularly in the younger population.


Publication metadata

Author(s): Lane LC, Kus A, Bednarczuk T, Bossowski A, Daroszewski J, Jurecka-Lubieniecka B, Cordell HJ, Pearce SHS, Cheetham T, Mitchell AL

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2020

Volume: 105

Issue: 9

Print publication date: 01/09/2020

Online publication date: 05/06/2020

Acceptance date: 01/06/2020

Date deposited: 06/08/2020

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: Oxford University Press

URL: https://doi.org/10.1210/clinem/dgaa347

DOI: 10.1210/clinem/dgaa347

PubMed id: 32501499


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