Association of CLTA-4 Gene Polymorphisms with Diabetes Mellitus: A Study Based on the Han Population of Northern China.

Objective: This study aimed to investigate the association of CLTA-4 gene polymorphism with Type 1 and 2 diabetes mellitus (DM) (T1DM and T2DM) in the Han population of northern China.

Methods: A total of 234 Chinese Han DM patients and 187 non-diabetic subjects were included in the study. Two gene polymorphisms of the CLTA-4, including CTLA-4+49A/G (rs231775) and CTLA4-318C/T (rs5742909), were studied using polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) analysis. Chi-square analysis and Student's -test were performed to determine the distribution of the gene polymorphism and alleles at the locus of CTLA4-318C/T and CTLA4+49A/G among T1DM and T2DM patients with or without diabetic ketosis (DK), diabetic nephropathy (DN) or autoantibodies (Ab).

Results: Our results indicated that the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G and CTLA4-318C/T loci of T1DM patients were not significantly different from those of the controls. However, the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G loci of T2DM patients were significantly different from the controls (P=0.024 for genotypes and P=0.004 for A and G alleles). Besides, the A and G alleles at the CTLA4-318C/T loci of T2DM DK+ patients showed significantly different distribution frequencies compared to those of the T2DM DK patients (P=0.001).

Conclusion: Our data suggest that the gene polymorphisms of CTLA-4, including CTLA-4+49A/G and CTLA4-318C/T, are important predictors of DM. CTLA-4 may be a susceptibility gene for T2DM. Patients with T2DM carrying the T allele at the CTLA4-318 C/T locus are more predisposed to diabetic ketosis.