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.
Institute of Pediatrics, University School of Medecine, Lodz, Poland. m.krokowski@alef.am.lodz.pl
M
M
Krokowski
J
J
Bodalski
A
A
Bratek
P
P
Machejko
S
S
Caillat-Zucman
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