Association of the T-cell regulatory gene CTLA4 with Graves' disease and autoimmune thyroid disease in the Japanese.
Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigen. The cytotoxic T-lymphocyte antigen-4 ( CTLA4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3'UTR of the CTLA4 gene, in which the three single-nucleotide polymorphisms (SNPs) CT60, JO31, and JO30 were strongly associated with AITD. In order to determine the association of the CTLA4 gene with AITD in the Japanese, case-control association analysis for the four SNPs of the CTLA4 gene using 380 AITD patients and 266 healthy controls was done. Among the SNPs examined, the SNP JO31 was most significantly associated with AITD in the Japanese, whereas the association of the JO30 with AITD was not observed. The frequency of the disease-susceptible G allele of the JO31 of the Japanese control was higher than that of the Caucasians (67.1% vs 50.2%); however, the G allele of the JO31 was associated with Graves' disease (GD) (67.1% vs 76.3%, P=0.0013) and AITD in the Japanese (67.1% vs 74.2%, P=0.0055). Furthermore, the G allele of the JO31 was associated with the increased risk for GD [ P=0.0051, odds ratio (OR)=1.7] and AITD ( P=0.016, OR=1.5) in a dominant model. These results suggested that the CTLA4 gene is involved in the susceptibility for GD and AITD in the Japanese.
Furugaki
Koichi
K
Department of Pathology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.|Department of Surgery and Oncology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Shirasawa
Senji
S
Department of Pathology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Ishikawa
Naofumi
N
Ito Hospital, Tokyo, Japan.
Ito
Kunihiko
K
Ito Hospital, Tokyo, Japan.
Ito
Koichi
K
Ito Hospital, Tokyo, Japan.
Kubota
Sumihisa
S
Kuma Hospital, Kobe, Japan.
Kuma
Kanji
K
Kuma Hospital, Kobe, Japan.
Tamai
Hajime
H
Kuma Hospital, Kobe, Japan.
Akamizu
Takashi
T
Translational Research Center, Kyoto University School of Medicine, Kyoto, Japan.
Hiratani
Hitomi
H
Translational Research Center, Kyoto University School of Medicine, Kyoto, Japan.
Tanaka
Masao
M
Department of Surgery and Oncology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Sasazuki
Takehiko
T
Department of Pathology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. sasazuki@ri.imcj.go.jp.
D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D007564:Japan; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013967:Thyroiditis, Autoimmune / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human