CTLA-4 single-nucleotide polymorphisms in a Caucasian population with schizophrenia.

Associations between a single-nucleotide polymorphism (SNP) in exon 1 of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene and schizophrenia in a Korean population have been previously described. The current study investigated whether a similar link occurs in a Caucasian population with schizophrenia. One hundred and twenty-two age- and sex-matched pairs of people with DSM-III-R diagnosis of schizophrenia and healthy controls were included in this study. Three previously described SNPs (from the promoter, exon 1 and 3' UTR) of the CTLA4 gene were analysed. In the entire sample, we detected no allelic or genotypic association for any of the three SNPs. Given documented gender differences in incidence of schizophrenia, we conducted separate analyses of male and female participants. In males, both the promoter region SNP (-318C/T) and the 3' UTR SNP demonstrated nominally significant association with schizophrenia. The 3' UTR SNP remained significant following correction for multiple testing (permuted P=0.046). In addition, all possible haplogenotypes showed significant association with disease in males with two--both containing the 3' UTR SNP--remaining significant following correction for the genotypic tests of all SNPs and haplogenotypes in males. These results suggest a role for the 3' UTR SNP and/or variants in high linkage disequilibrium with this SNP in the pathogenesis of schizophrenia.