OBJECTIVETo investigate the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene A/G polymorphism with susceptibility to diabetes mellitus in Han Chinese.

METHODSAn A/G transition at position 49 of exon 1 was analyzed in 31 patients with type 1 diabetes, 31 patients with type 2 diabetes, and 36 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis.

RESULTSA highly significant increase in the frequency of the G allele was seen in patients with type 1 diabetes compared with controls (66.1 % vs. 34.7%, respectively; P < 0.0005; OR = 3.670) . This reflected an increase in the GG genotype in patients (48.4% vs. 22.2%, respectively; P =0.025; OR =3.281) and a significant decrease in the AA genotype (16.1 % vs. 52.8%, respectively; P = 0.002). The allele frequencies of A and G in patients with type 2 diabetes were not significantly different from controls(A/G, 50.0/50.0% vs. 65.3/34.7%; P = not significant) . The distribution of genotype, however, differed significantly. This difference reflected an increase in the AG genotype in patients (54.8% vs.25.0%, respectively; P=0.012; OR=3.643) and a decrease in the AA genotype (22.6% vs. 52.8%, respectively; P=0.011).

CONCLUSIONSCTLA-4 49 AA is protective from diabetes mellitus, whereas, CTLA-4 49 G allele (both as homozygotes and as heterozygotes ) confers an increased risk of diabetes mellitus.