The association of thyroid peroxidase antibody risk loci with susceptibility to and phenotype of Graves' disease.

Détails

ID Serval
serval:BIB_9FB86DFF5227
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The association of thyroid peroxidase antibody risk loci with susceptibility to and phenotype of Graves' disease.
Périodique
Clinical endocrinology
Auteur⸱e⸱s
Kuś A., Szymański K., Peeters R.P., Miśkiewicz P., Porcu E., Pistis G., Sanna S., Naitza S., Płoski R., Medici M., Bednarczuk T.
ISSN
1365-2265 (Electronic)
ISSN-L
0300-0664
Statut éditorial
Publié
Date de publication
10/2015
Peer-reviewed
Oui
Volume
83
Numéro
4
Pages
556-562
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Despite great progress, the genetic basis of Graves' disease (GD) remains poorly understood. Recently, a population-based genomewide association study (GWAS) identified five novel loci (ATXN2/SH2B3, MAGI3, BACH2, TPO and KALRN) as significantly associated with the presence of thyroid peroxidase autoantibodies (TPOAbs), whereas several other loci showed suggestive association.
In this study, we investigated 16 single nucleotide polymorphisms (SNPs) associated with TPOAbs for the association with susceptibility to and phenotype of GD in a cohort of 647 patients with GD and 769 controls from a Polish Caucasian population.
SNPs within/near HCP5 (rs3094228, P = 1·6 × 10(-12) , OR = 1·88), MAGI3 (rs1230666, P = 1·9 × 10(-5) , OR = 1·51) and ATXN2/SH2B3 (rs653178, P = 0·0015, OR = 1·28) loci were significantly associated with susceptibility to GD. Allele frequencies differed significantly in subgroups of patients with GD stratified by age of GD onset for HCP5 (P = 0·0014, OR = 1·50) and showed a suggestive difference for MAGI3 (P = 0·0035, OR = 1·50) SNPs. Although rs11675434 located near TPO showed no association with GD susceptibility, it was significantly associated with the presence of clinically evident Graves' ophthalmopathy (GO, P = 5·2 × 10(-5) , OR = 1·64), and this effect was independent from smoking status, age of GD onset and gender.
This is the first study showing an association of the ATXN2/SH2B3 locus with susceptibility to GD. Furthermore, we observed a novel significant association within the HLA region at a SNP located near HCP5 and confirmed the association of the MAGI3 locus with GD susceptibility. HCP5 and MAGI3 SNPs were further correlated with age of GD onset. Finally, we identified TPO as a new susceptibility locus for GO.
Mots-clé
Adult, Autoantibodies/genetics, Autoantigens/immunology, Female, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Graves Disease/genetics, Graves Disease/immunology, Humans, Iodide Peroxidase/immunology, Iron-Binding Proteins/immunology, Male, Middle Aged, Polymorphism, Single Nucleotide/genetics
Pubmed
Web of science
Création de la notice
18/01/2021 22:32
Dernière modification de la notice
19/01/2021 7:26
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