Ontology highlight
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 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.
SUBMITTER: Lane LC
PROVIDER: S-EPMC7382372 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Lane Laura Claire LC Kuś Aleksander A Bednarczuk Tomasz T Bossowski Artur A Daroszewski Jacek J Jurecka-Lubieniecka Beata B Cordell Heather Jane HJ Pearce Simon Henry Schofield SHS Cheetham Timothy T Mitchell Anna Louise AL
The Journal of clinical endocrinology and metabolism 20200901 9
<h4>Context</h4>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.<h4>Objective</h4>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.<h4>Design and participants</h4>rs3 ...[more]