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

Lane, Laura C; Kuś, Aleksander; Bednarczuk, Tomasz; Bossowski, Artur; Daroszewski, Jacek; Jurecka‐Lubieniecka, Beata; Cordell, Heather J.; Pearce, Simon H. S.; Cheetham, Timothy; Mitchell, Anna L.

doi:10.1210/clinem/dgaa347

Cited by 12 publications

(8 citation statements)

References 47 publications

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“…TG and TSHR) (13,14,15). HCP5 polymorphisms have been associated with a younger age at GD onset (16,17). GD is associated with the occurrence of other autoimmune disorders such as type I diabetes mellitus, celiac disease and vitiligo and is more common in Down syndrome (4,18).…”

Section: Definitive Treatment In Pediatric Gd -Radioiodine (Rai)mentioning

confidence: 99%

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

Mooij

Cheetham

Verburg

et al. 2022

European Thyroid Journal

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Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

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Section: Definitive Treatment In Pediatric Gd -Radioiodine (Rai)mentioning

confidence: 99%

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

Mooij

Cheetham

Verburg

et al. 2022

European Thyroid Journal

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“…Younger GD patients tend to have more severe hyperthyroidism at presentation when compared to adults [ 9 ] and this may be partly related to the nature of the underlying immune dysfunction. Recent data have shown that the human leukocyte antigen (HLA) complex P5 (HCP5) polymorphism is independently associated with GD susceptibility and age of onset [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

How to use thionamide anti-thyroid drug in the young– what’s new?

Cheetham

2021

Thyroid Res

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The excess thyroid hormone secretion that characterises Graves’ disease (GD) is generated when stimulatory antibodies bind to the thyroid stimulating hormone receptor on the follicular cell of the thyroid gland.This underlying mechanism cannot easily be abolished and the mainstay of Graves’ disease (GD) management in the young remains thionamide anti-thyroid drug (ATD). Unfortunately, GD will usually recur after a 2 or 3 year course of ATD, even when the stimulatory antibody titres have fallen. The diagnosis of GD therefore usually signals the start of a lengthy period of out-patient assessments and associated venepuncture. Careful, more protracted administration of ATD may increase the likelihood of longer-term remission and reduce the likelihood of the patient developing ATD side-effects. An understanding of how best to use ATD and an awareness of the less well-known consequences of GD and its’ treatment - such as excessive weight-gain and long-term hypothyroidism – are also of fundamental importance.Recent clinical studies have shed light on how best to manage the young patient with GD and the associated new information will help to answer some of the questions posed by the young person and their family at diagnosis. This new knowledge is the focus of this article about ATD therapy in the young.

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“…The locus with the strongest evidence for a role in gout was CNVR1, which is dominated by deletion. Genetic (SNV) associations identified by GWAS for immune-mediated disease have been reported at this locus, including HIV infection ( 32 ) and autoimmune diseases such as Grave’s disease ( 33 ) and systemic lupus erythematosus ( 34 ). CNVs that overlap CNVR1 have been reported to be associated with nasopharyngeal carcinoma predisposition ( 35 , 36 ), type 1 diabetes ( 37 ) and schizophrenia or bipolar disorder ( 38 ) and, now, gout.…”

Section: Discussionmentioning

confidence: 99%

A Polynesian-specific copy number variant encompassing the MICA gene associates with gout

Wang

Cadzow

Bixley

et al. 2022

Human Molecular Genetics

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Gout is of particularly high prevalence in the Māori and Pacific (Polynesian) populations of Aotearoa New Zealand (NZ). Here, we investigated the contribution of common population-specific CNV to gout in the Aotearoa NZ Polynesian population. Microarray-generated genome-wide genotype data from Aotearoa NZ Polynesian individuals with (n = 1196) and without (n = 1249) gout were analyzed. Comparator population groups were 552 individuals of European ancestry and 1962 of Han Chinese ancestry. Levels of circulating MHC Class I Polypeptide-related sequence A (MICA) were measured by ELISA. Fifty-four CNV regions (CNVRs) appearing in at least 10 individuals were detected, of which seven common CNVRs were specific to or amplified in Polynesian people. A burden test of these seven revealed associations of insertion/deletion with gout (OR = 1.80 [1.01; 3.22], P = 0.046). Individually testing of the seven CNVRs for association with gout revealed nominal association of CNVR1 with gout in Western Polynesian (Chr6: 31.36–31.45 Mb, OR = 1.72 [1.03; 2.92], P = 0.04), CNVR6 in the meta-analyzed Polynesian sample sets (Chr1: 196.75–196.92 Mb, OR = 1.86 [1.16; 3.00], P = 0.01) and CNVR9 in Western Polynesian (Chr1: 189.35–189.54 Mb, OR = 2.75 [1.15; 7.13], P = 0.03). Analysis of European gout genetic association data demonstrated a signal of association at the CNVR1 locus that was an expression QTL for MICA. The most common CNVR (CNVR1) includes deletion of the MICA gene, encoding an immunomodulatory protein. Expression of MICA was reduced in the serum of individuals with the deletion. In summary, we provide evidence for the association of CNVR1 containing MICA with gout in Polynesian peoples, implicating class I MHC-mediated antigen presentation in gout.

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

Cited by 12 publications

References 47 publications

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

2022 European Thyroid Association Guideline for the management of pediatric Graves’ disease

How to use thionamide anti-thyroid drug in the young– what’s new?

A Polynesian-specific copy number variant encompassing the MICA gene associates with gout

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