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

Abstract 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 inve...

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Vydané v:	The journal of clinical endocrinology and metabolism Ročník 105; číslo 9; s. e3277 - e3284
Hlavní autori:	Lane, Laura Claire, Kuś, Aleksander, Bednarczuk, Tomasz, Bossowski, Artur, Daroszewski, Jacek, Jurecka-Lubieniecka, Beata, Cordell, Heather Jane, Pearce, Simon Henry Schofield, Cheetham, Timothy, Mitchell, Anna Louise
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	US Oxford University Press 01.09.2020 Copyright Oxford University Press
Predmet:	Adolescent Adult Age Age of Onset Aged Aged, 80 and over Alleles Case-Control Studies Child Child, Preschool Cohort Studies Comparative analysis Consortia Disease susceptibility Drb1 protein Female Gene Frequency Gene polymorphism Genetic aspects Genetic Association Studies Genetic polymorphisms Genetic Predisposition to Disease Graves disease Graves Disease - epidemiology Graves Disease - genetics Haplotypes Histocompatibility antigen HLA Histocompatibility antigens HLA histocompatibility antigens Humans Introns - genetics Linkage disequilibrium Male Meta-analysis Middle Aged Online Only Poland - epidemiology Polymorphism, Single Nucleotide RNA, Long Noncoding - genetics Susceptibility Trusts and trustees United Kingdom - epidemiology Young Adult Poland United Kingdom United Kingdom > UK Graves disease meta-analysis polymorphism thyroid autoimmune genotyping
ISSN:	0021-972X, 1945-7197, 1945-7197
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Shrnutí:	Abstract 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 DRB10301 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 DRB10301. 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0021-972X 1945-7197 1945-7197
DOI:	10.1210/clinem/dgaa347