Interactions between programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) gene polymorphisms in type 1 diabetes.Diabetes Res Clin Pract 2009; 83(3):289-94DR
To explore the contribution of the PD-1 gene polymorphisms involved in T1D as well as the relationship between the PD-1/CTLA-4 genes and soluble CTLA-4 concentrations.
PATIENTS AND METHODS
261 incident cases of T1D and 280 healthy children less 15 years old were included in this study. Haplotypes for polymorphisms of the PD-1 and CTLA-4 genes were determined by PCR and RFLP methods. Screening for soluble CTLA-4 was done using an ELISA assay. Statistical analysis was performed using the online SHESIS package.
Our results show that sCTLA-4 levels were higher in T1D than in controls (2.99+/-1.7 ng/ml versus 1.43+/-0.31 ng/ml, p<0.001). The allele dosage of CTLA-4 on PD-1 haplotypes, showing a significant modified effect of G carriers over AA genotype on the sCTLA-4 concentrations (5.48+/-2.09 ng/ml versus 3.27+/-1.30 ng/ml, p<0.03 in T-C haplotype) and (1.92+/-0.79 ng/ml versus 3.41+/-1.10 ng/ml, p<0.02 in C-T haplotype).
Consistent with the higher serum sCTLA-4 levels observed in other autoimmune diseases, our results suggest that sCTLA-4 is elevated in T1D. Our data suggest a possible gene dosage effect of "G"CTLA-4 carriers on sCTLA-4 over the possible protective or susceptible effect conferred by PD-1 haplotypes.