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01-12-2012

Associations Between Autoimmune Thyroid Disease Prognosis and Functional Polymorphisms of Susceptibility Genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, Previously Revealed in Genome-wide Association Studies

Authors: Naoya Inoue, Mikio Watanabe, Hiroya Yamada, Kazuya Takemura, Fumiaki Hayashi, Noriko Yamakawa, Maiko Akahane, Yu Shimizuishi, Yoh Hidaka, Yoshinori Iwatani

Published in: Journal of Clinical Immunology | Issue 6/2012

Abstract

Purpose

Genome-wide association studies have revealed several susceptibility genes among patients with autoimmune thyroid disease (AITD), including CTLA4, PTPN22, FCRL3, and ZFAT. However, any possible association between these genes and AITD prognosis remains unknown. The objective of this study was to identify associations between polymorphisms of these genes and AITD prognosis.

Methods

We genotyped functional polymorphisms, including CTLA4 CT60, CTLA4 +49A/G, CTLA4 -1147C/T, CTLA4 -318C/T, PTPN22 -1123C/G, PTPN22 SNP37, CD40 -1C/T, FCRL3 -169C/T, ZFAT Ex9b-SNP10, and ZFAT Ex9b-SNP2, in 197 AITD patients carefully selected from 456 registered AITD patients, and 86 control subjects. The restriction fragment length polymorphism method was used for genotyping.

Results

The CD40 -1CC genotype and C allele were significantly more frequent in patients with Graves’ disease (GD) in remission than in those with intractable GD (P = 0.041 and P = 0.031, respectively). The FCRL3 -169TT genotype was significantly less frequent in patients with intractable GD than in those with GD in remission (P = 0.0324). For a ZFAT Ex9b-SNP10 polymorphism, the TT genotype and T allele were significantly more frequent in patients with severe Hashimoto’s disease (HD) than in those with mild HD (P = 0.0029 and P = 0.0049, respectively). For a CTLA4 CT60 polymorphism, the antithyrotropin receptor antibody levels at the onset of GD were significantly higher in those with the GG genotype than in those with other genotypes (P = 0.0117).

Conclusions

CD40 and FCRL3 gene polymorphisms were associated with GD intractability, and ZFAT polymorphism was associated with HD severity but not its development.

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Title: Associations Between Autoimmune Thyroid Disease Prognosis and Functional Polymorphisms of Susceptibility Genes, CTLA4, PTPN22, CD40, FCRL3, and ZFAT, Previously Revealed in Genome-wide Association Studies
Authors: Naoya Inoue
Mikio Watanabe
Hiroya Yamada
Kazuya Takemura
Fumiaki Hayashi
Noriko Yamakawa
Maiko Akahane
Yu Shimizuishi
Yoh Hidaka
Yoshinori Iwatani
Publication date: 01-12-2012
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 6/2012
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-012-9721-0

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Plasma concentrations of growth arrest specific protein 6 and the soluble form of its tyrosine kinase receptor Axl in patients with Systemic lupus erythematosus and Behçets disease

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials