PMID- 32501499
OWN - NLM
STAT- MEDLINE
DCOM- 20210223
LR  - 20240229
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 105
IP  - 9
DP  - 2020 Sep 1
TI  - An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to 
      Graves Disease in UK and Polish Cohorts.
PG  - e3277-84
LID - dgaa347 [pii]
LID - 10.1210/clinem/dgaa347 [doi]
AB  - 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 x 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 x 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 x 10-5) and age of onset (P allele=5.63 x 10-8). Haplotype 
      analysis demonstrated that rs3094228 is associated with age of GD onset 
      (P = 2.39 x 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.
CI  - (c) Endocrine Society 2020. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Lane, Laura Claire
AU  - Lane LC
AD  - Translational and Clinical Research Institute, Newcastle University, 
      Newcastle-upon-Tyne, UK.
AD  - Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
AD  - Department of Paediatric Endocrinology, The Great North Children's Hospital, 
      Newcastle-upon-Tyne, UK.
FAU - Kus, Aleksander
AU  - Kus A
AD  - Department of Internal Medicine and Endocrinology, Medical University of Warsaw, 
      Warsaw, Poland.
FAU - Bednarczuk, Tomasz
AU  - Bednarczuk T
AD  - Department of Internal Medicine and Endocrinology, Medical University of Warsaw, 
      Warsaw, Poland.
FAU - Bossowski, Artur
AU  - Bossowski A
AD  - Department of Pediatrics, Endocrinology and Diabetes with a Cardiology Unit, 
      Medical University of Bialystok, Bialystok, Poland.
FAU - Daroszewski, Jacek
AU  - Daroszewski J
AD  - Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical 
      University, Wroclaw, Poland.
FAU - Jurecka-Lubieniecka, Beata
AU  - Jurecka-Lubieniecka B
AD  - Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie 
      Institute - Oncology Center, Gliwice Branch, Gliwice, Poland.
FAU - Cordell, Heather Jane
AU  - Cordell HJ
AD  - Population Health Sciences Institute, Newcastle University, Newcastle-upon-Tyne, 
      UK.
FAU - Pearce, Simon Henry Schofield
AU  - Pearce SHS
AD  - Translational and Clinical Research Institute, Newcastle University, 
      Newcastle-upon-Tyne, UK.
AD  - Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
FAU - Cheetham, Timothy
AU  - Cheetham T
AD  - Translational and Clinical Research Institute, Newcastle University, 
      Newcastle-upon-Tyne, UK.
AD  - Department of Paediatric Endocrinology, The Great North Children's Hospital, 
      Newcastle-upon-Tyne, UK.
FAU - Mitchell, Anna Louise
AU  - Mitchell AL
AD  - Translational and Clinical Research Institute, Newcastle University, 
      Newcastle-upon-Tyne, UK.
AD  - Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK.
LA  - eng
GR  - G0500783/MRC_/Medical Research Council/United Kingdom
GR  - MR/S001611/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (HCP5 long noncoding RNA, human)
RN  - 0 (RNA, Long Noncoding)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Female
MH  - Gene Frequency
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Graves Disease/*epidemiology/*genetics
MH  - Humans
MH  - Introns/genetics
MH  - Male
MH  - Middle Aged
MH  - Poland/epidemiology
MH  - *Polymorphism, Single Nucleotide
MH  - RNA, Long Noncoding/*genetics
MH  - United Kingdom/epidemiology
MH  - Young Adult
PMC - PMC7382372
OTO - NOTNLM
OT  - Graves disease
OT  - autoimmune
OT  - genotyping
OT  - meta-analysis
OT  - polymorphism
OT  - thyroid
EDAT- 2020/06/06 06:00
MHDA- 2021/02/24 06:00
PMCR- 2020/06/05
CRDT- 2020/06/06 06:00
PHST- 2019/12/12 00:00 [received]
PHST- 2020/06/01 00:00 [accepted]
PHST- 2020/06/06 06:00 [pubmed]
PHST- 2021/02/24 06:00 [medline]
PHST- 2020/06/06 06:00 [entrez]
PHST- 2020/06/05 00:00 [pmc-release]
AID - 5851730 [pii]
AID - dgaa347 [pii]
AID - 10.1210/clinem/dgaa347 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3277-84. doi: 10.1210/clinem/dgaa347.