CTLA4 GENE POLYMORPHISM CONFERS SUSCEPTIBILITY TO GRAVES-DISEASE IN JAPANESE

Susceptibility to Graves' disease (GD) is determined by environmental and genetic factors. The genetic susceptibility to GD is conferred by genes in the human leukocyte antigen (HLA), and several other genes un linked to HLA are thought to contribute to the development of GD. Thre e recent papers described the association of GD with the CTLA-4 gene. CTLA-4 is a candidate gene for T-cell mediated autoimmune diseases bec ause it is a negative regulator of T-cell proliferation. As CTLA-4 ass ociation with GD may be influenced by the racial composition of the po pulation, it is important to study it in other ethnic groups. We inves tigated the distribution of CTLA-4 gene polymorphism in 153 Japanese p atients with GD (35 males and 118 females) and 200 controls (96 males and 104 females). An A/G transition at position 49 of exon 1 was analy zed by the polymerase chain reaction-restriction fragment length polym orphism (PCR-RFLP) method. The distribution of genotype frequencies di ffers between GD and controls (chi(2) = 9.46, 2 degrees of freedom, p < 0.01). The presence of at least one G allele (GG or AG) conferred an odds ratio of 2.64 (95% CI = 1.92-3.36). The present study supported the association of the CTLA-4 gene with GD in Japanese and showed that the CTLA4 gene could be one of the non-HLA linked susceptibility gene s for GD.