Prevalence of CTLA-4 polymorphism A49G in Ashkenazi Jews

Type 1 diabetes has been associated with numerous genetic loci. One locus, IDD12, includes the gene for cytotoxic T lymphocyte antigen (CTLA-4). A polymorphism at position 49 in the CTLA-4 gene, causing a substitution of Thr --> Ala, has been associated with various autoimmune diseases, including diabetes. The frequency of the polymorphism in European and Oriental populations has been recorded, but the frequency among different ethnic groups within the United States has yet to be established. In the present study, we analyzed 100 DNA samples from Ashkenazi Jews to determine the polymorphism's prevalence in that population. The A/A genotype was found in 49% of individuals, 41% were heterozygous A/G, and 10% possessed the G/G genotype. The prevalence of the A/A genotype in Ashkenazi Jewish population is the highest reported to date. The incidence of the homozygous G/G genotype within Spanish controls, 8.8%, is the lowest, followed by the Ashkenazi general population. The frequency of the non-diabetes-associated A/A genotype shows a similarity to the frequency of the diabetes-susceptible HLA haplotype, DR4-DQ8. The low prevalence of the autoimmune-associated G allele among Ashkenazi Jewish and Spanish populations may explain a lower than expected incidence of diabetes in HLA-susceptible populations.