PMID- 19731979
OWN - NLM
STAT- MEDLINE
DCOM- 20091123
LR  - 20131121
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Linking)
VI  - 19
IP  - 9
DP  - 2009 Sep
TI  - Association of polymorphism at position 49 in exon 1 of the cytotoxic 
      T-lymphocyte-associated factor 4 gene with Graves' disease refractory to medical 
      treatment, but not with amiodarone-associated thyroid dysfunction.
PG  - 975-81
LID - 10.1089/thy.2009.0066 [doi]
AB  - BACKGROUND: Recently, the G allele of the cytotoxic T-lymphocyte-associated 
      factor 4 (CTLA-4) exon 1 single-nucleotide polymorphism (CTLA-4 A/G(49)) has been 
      identified as the most informative marker in patients with Graves' disease. 
      Patients with the G/G genotype are refractory to medical treatment and frequently 
      relapse after discontinuation of antithyroid drugs. Therefore, we analyzed CTLA-4 
      A/G(49) in patients who had been treated with (131)I. Further, a preliminary 
      report has suggested that amiodarone-associated thyroid dysfunction (AATD) has a 
      relationship with human leukocyte antigen (HLA) class I and class II. METHOD: 
      CTLA-4 genotypes in exon 1 (A/G(49)) and CT60 were analyzed in 415 Japanese 
      patients with Graves' disease and 65 patients with AATD. RESULTS: The frequencies 
      of the G alleles and G/G genotype at the both polymorphisms were significantly 
      higher in Graves' patients compared with normal subjects. Compared with CT60, the 
      frequencies of the G alleles and G/G genotypes at the A/G(49) were more 
      significantly higher in patients with persistently positive thyrotropin receptor 
      antibody despite >5 years of antithyroid drug therapy, compared with those whose 
      thyrotropin receptor antibody became negative in <5 years (p < 0.0001). 
      Consequently, the frequencies of the G/G genotype and G allele at the A/G(49) 
      were also significantly higher in patients with Graves' disease who received 
      (131)I therapy (p < 0.05). However, there was no significant difference in the 
      A/G polymorphisms in the 65 patients with AATD. CONCLUSIONS: The G/G genotype in 
      exon 1 (A/G(49)) is frequently expressed in Graves' disease patients who are 
      refractory to antithyroid drug treatment. Therefore, the G/G genotype in A/G(49) 
      would be a useful predictor of Graves' patients who are suitable for radioiodine 
      therapy. Although the number of analyzed patients was small, our preliminary data 
      suggest that the CTLA-4 gene polymorphisms might be unassociated with AATD.
FAU - Kimura, Hironari
AU  - Kimura H
AD  - Department of Internal Medicine, Institute of Clinical Endocrinology, Tokyo 
      Women's Medical University, Tokyo, Japan.
FAU - Kato, Yoshiyuki
AU  - Kato Y
FAU - Shimizu, Satoru
AU  - Shimizu S
FAU - Takano, Kazue
AU  - Takano K
FAU - Sato, Kanji
AU  - Sato K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Antigens, CD)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - N3RQ532IUT (Amiodarone)
SB  - IM
MH  - Adult
MH  - Amiodarone/*adverse effects
MH  - Antigens, CD/*genetics
MH  - CTLA-4 Antigen
MH  - Female
MH  - Graves Disease/drug therapy/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Thyroid Diseases/*chemically induced
EDAT- 2009/09/08 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/09/08 06:00
PHST- 2009/09/08 06:00 [entrez]
PHST- 2009/09/08 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 10.1089/thy.2009.0066 [doi]
PST - ppublish
SO  - Thyroid. 2009 Sep;19(9):975-81. doi: 10.1089/thy.2009.0066.