Polymorphism located in promoter of CTLA-4 gene is not associated with type 1 diabetes in contrast to A→G transition within exon 1

The CTLA-4 gene located on chromosome 2q33 is involved in susceptibility to insulin-dependent diabetes mellitus (IDDM), especially concerning exon 1 transition of the gene (A-->G; +49 position; Ita I). Recently, a novel polymorphism in the promoter region of the CTLA-4 gene (C-->T; -318 position; Mse I) has been reported. This study aimed to compare the relation between both polymorphic sites of the CTLA-4 gene and IDDM in the Polish population. Of 207 diabetic patients 36 (17.4%) exhibited CT and two (1%) the TT variant compared with 46 (20.6%) and 1 (0.5%) in 223 controls, respectively (no significant differences). The IDDM patients (73.4%) carried the Ita I polymorphism, among which 49.8% exhibited both alleles (AG) and 23.7% the GG genotype (G-allele frequency 48.6%). Results showed that 59.2% (p = 0.003; RR = 1.9) of controls showed Ita I polymorphism including 51.6% heterozygous and 7.6% (p < 10(-5); RR = 3.8) homozygous individuals (G-allele frequency 33.4%; p < 10(-5); RR = 1.9). Thus Mse I polymorphism in the promoter region of the CTLA-4 gene is unlikely to contribute to putative genetic susceptibility to IDDM in contrast to exon 1 transition, which may be involved in IDDM susceptibility.