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.
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.
Koichi
K
Furugaki
Department of Pathology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Senji
S
Shirasawa
Ito Hospital, Tokyo, Japan.
Naofumi
N
Ishikawa
Ito Hospital, Tokyo, Japan.
Kunihiko
K
Ito
Ito Hospital, Tokyo, Japan.
Koichi
K
Ito
Kuma Hospital, Kobe, Japan.
Sumihisa
S
Kubota
Kuma Hospital, Kobe, Japan.
Kanji
K
Kuma
Kuma Hospital, Kobe, Japan.
Hajime
H
Tamai
Translational Research Center, Kyoto University School of Medicine, Kyoto, Japan.
Takashi
T
Akamizu
Translational Research Center, Kyoto University School of Medicine, Kyoto, Japan.
Hitomi
H
Hiratani
Department of Surgery and Oncology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Masao
M
Tanaka
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.
Takehiko
T
Sasazuki
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