CTLA-4 gene polymorphism is associated with predisposition to IDDM in a population from central Poland

• Published in: Diabetes & metabolism Vol. 24; no. 3; p. 241
• Main Authors: Krokowski, M, Bodalski, J, Bratek, A, Machejko, P, Caillat-Zucman, S
• Format: Journal Article
• Language: English
• Published: France 01.06.1998
• Subjects: Adolescent; Case-Control Studies; Causality; Child; Child, Preschool; Chromosome Mapping; Diabetes Mellitus, Type 1 - genetics; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Infant; Poland; Polymorphism, Genetic; T-Lymphocytes, Cytotoxic - physiology; Poland
• ISSN: 1262-3636

Susceptibility to insulin-dependent diabetes mellitus (IDDM) is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. The candidate genes include the cytoxic T-lymphocyte associated-4 (CTLA-4) gene located on chromosome 2q33, which encodes a cell surface molecule providing a negative signal for T-cell activation. We investigated CTLA-4 exon 1 polymorphism (position 49 A/G) in 192 IDDM children and 136 healthy controls from Central Poland, using allele-specific hybridisation. The CTLA-4/G allele was found on 56.0% of chromosomes in IDDM patients as compared to 43.4% in controls (p = 0.002), mostly in homozygous form (31.2% in patients vs 15.4% in controls, p = 0.002). This difference was even more pronounced in non-DRB1*03/non-DRB1*04 IDDM patients (G/G genotype frequency: 35.0% of IDDM patients vs 12.3% of controls, p = 0.04). Our data indicate that CTLA-4 exon 1 position 49 A/G dimorphism was significantly associated with predisposition to IDDM in our Central Poland population, particularly in patients lacking the strongly predisposing DRB1 alleles.