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


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).


CONCLUSIONS
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.
Momin
Scherezade
S
University of Michigan, Ann Arbor, MI, USA.
Flores
Sylvia
S
Angel B
Bárbara
B
Codner D
Ethel
E
Carrasco P
Elena
E
Perez-Bravo
Francisco
F
D000293:Adolescent; D015703:Antigens, CD / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D060908:CTLA-4 Antigen; D002648:Child; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007330:Insulin Antibodies / Q000097:blood; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D061026:Programmed Cell Death 1 Receptor; D012016:Reference Values
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007141:Immunoglobulin Fc Fragments; D007330:Insulin Antibodies; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D004247:DNA