Interactions between programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) gene polymorphisms in type 1 diabetes

Abstract

Aim 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. Results 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). Conclusion 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.