Association of a C/T Single-Nucleotide Polymorphism in the 5' Untranslated Region of the CD40 Gene with Graves' Disease in Japanese

Context: Graves' disease (GD) is caused by an interplay of genetic factors and environmental triggers. Recently, a susceptibility locus for GD was mapped to chromosome 20q11 (GD-2). Furthermore, a novel single nucleotide polymorphism (SNP) in the CD40 gene, which is located in 20q11, was found to be associated and linked with GD in Caucasians and in Koreans. Objectives: To examine a C/T SNP in the 5' untranslated region of the CD40 gene (CD40-E1SNP) for association with autoimmune thyroid diseases (AITDs) in a Japanese dataset. Design, setting, and patients: Case-control association studies were performed using the CD40-E1SNP. We studied 485 Japanese patients with AITD (301 with GD, 184 with Hashimoto's thyroiditis [HT]) and 177 matched Japanese control subjects in association studies. Main outcome: Frequencies of genotypes and alleles of the CD40- E1SNP. Results: The distribution of genotype frequencies differed significantly between patients with GD and controls in a dominant manner (p = 0.039). The CC+CT genotypes of the CD40-E1SNP were associated with the increased risk for GD (p = 0.015, odds ratio [OR] = 1.9). In contrast, no differences in genotype frequencies were observed between HT patients and controls for the CD40-E1SNP. Conclusion: These results suggested that the CD40 gene is involved insusceptibility for GD in the Japanese.