CTLA-4 gene polymorphism is associated with predisposition to IDDM in a population from central Poland.
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.
Krokowski
M
M
Institute of Pediatrics, University School of Medecine, Lodz, Poland. m.krokowski@alef.am.lodz.pl
Bodalski
J
J
Bratek
A
A
Machejko
P
P
Caillat-Zucman
S
S
D000293:Adolescent; D016022:Case-Control Studies; D015984:Causality; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007223:Infant; D011044:Poland; D011110:Polymorphism, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains