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...

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Published in:	Diabetes research and clinical practice Vol. 83; no. 3; pp. 289 - 294
Main Authors:	Momin, Scherezade, Flores, Sylvia, Angel B, Bárbara, Codner D, Ethel, Carrasco P, Elena, Perez-Bravo, Francisco
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier Ireland Ltd 01-03-2009
Subjects:	Adolescent Antigens, CD - blood Antigens, CD - genetics Antigens, CD - metabolism Apoptosis Regulatory Proteins - genetics Autoantibodies - blood Child CTLA-4 CTLA-4 Antigen Diabetes Mellitus, Type 1 - blood Diabetes Mellitus, Type 1 - genetics Diabetes Mellitus, Type 1 - immunology DNA - genetics DNA - isolation & purification Endocrinology & Metabolism Female Genetic epidemiology Genotype Humans Immunoglobulin Fc Fragments - genetics Insulin Antibodies - blood Male PD-1 gene Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Restriction Fragment Length Programmed Cell Death 1 Receptor Reference Values Type 1 diabetes CTLA-4 Genetic epidemiology Type 1 diabetes PD-1 gene
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0168-8227 1872-8227
DOI:	10.1016/j.diabres.2008.12.003