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

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1243-1252
Number of pages10
JournalJournal of Clinical Immunology
Volume32
Issue number6
DOIs
Publication statusPublished - 01-12-2012

Fingerprint

Genome-Wide Association Study
Graves Disease
Thyroid Diseases
Autoimmune Diseases
Hashimoto Disease
Genotype
Genes
Alleles
Restriction Fragment Length Polymorphisms
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Inoue, Naoya ; Watanabe, Mikio ; Yamada, Hiroya ; Takemura, Kazuya ; Hayashi, Fumiaki ; Yamakawa, Noriko ; Akahane, Maiko ; Shimizuishi, Yu ; Hidaka, Yoh ; Iwatani, Yoshinori. / 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. In: Journal of Clinical Immunology. 2012 ; Vol. 32, No. 6. pp. 1243-1252.
@article{8aa3bf1b018f435e9efb9eb3e6b80530,
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",
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.",
author = "Naoya Inoue and Mikio Watanabe and Hiroya Yamada and Kazuya Takemura and Fumiaki Hayashi and Noriko Yamakawa and Maiko Akahane and Yu Shimizuishi and Yoh Hidaka and Yoshinori Iwatani",
year = "2012",
month = "12",
day = "1",
doi = "10.1007/s10875-012-9721-0",
language = "English",
volume = "32",
pages = "1243--1252",
journal = "Journal of Clinical Immunology",
issn = "0271-9142",
publisher = "Springer New York",
number = "6",

}

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

In: Journal of Clinical Immunology, Vol. 32, No. 6, 01.12.2012, p. 1243-1252.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Inoue, Naoya

AU - Watanabe, Mikio

AU - Yamada, Hiroya

AU - Takemura, Kazuya

AU - Hayashi, Fumiaki

AU - Yamakawa, Noriko

AU - Akahane, Maiko

AU - Shimizuishi, Yu

AU - Hidaka, Yoh

AU - Iwatani, Yoshinori

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878242161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878242161&partnerID=8YFLogxK

U2 - 10.1007/s10875-012-9721-0

DO - 10.1007/s10875-012-9721-0

M3 - Article

C2 - 22706687

AN - SCOPUS:84878242161

VL - 32

SP - 1243

EP - 1252

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

SN - 0271-9142

IS - 6

ER -