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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

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.

Authors+Show Affiliations

University of Michigan, Ann Arbor, MI, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19147248

Citation

Momin, Scherezade, et al. "Interactions Between Programmed Death 1 (PD-1) and Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) Gene Polymorphisms in Type 1 Diabetes." Diabetes Research and Clinical Practice, vol. 83, no. 3, 2009, pp. 289-94.
Momin S, Flores S, Angel B B, et al. 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):289-94.
Momin, S., Flores, S., Angel B, B., Codner D, E., Carrasco P, E., & Perez-Bravo, F. (2009). Interactions between programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) gene polymorphisms in type 1 diabetes. Diabetes Research and Clinical Practice, 83(3), pp. 289-94. doi:10.1016/j.diabres.2008.12.003.
Momin S, et al. 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):289-94. PubMed PMID: 19147248.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between programmed death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) gene polymorphisms in type 1 diabetes. AU - Momin,Scherezade, AU - Flores,Sylvia, AU - Angel B,Bárbara, AU - Codner D,Ethel, AU - Carrasco P,Elena, AU - Perez-Bravo,Francisco, Y1 - 2009/01/14/ PY - 2008/08/02/received PY - 2008/11/19/revised PY - 2008/12/02/accepted PY - 2009/1/17/entrez PY - 2009/1/17/pubmed PY - 2009/5/16/medline SP - 289 EP - 94 JF - Diabetes research and clinical practice JO - Diabetes Res. Clin. Pract. VL - 83 IS - 3 N2 - 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. SN - 1872-8227 UR - https://www.unboundmedicine.com/medline/citation/19147248/Interactions_between_programmed_death_1__PD_1__and_cytotoxic_T_lymphocyte_antigen_4__CTLA_4__gene_polymorphisms_in_type_1_diabetes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8227(08)00604-9 DB - PRIME DP - Unbound Medicine ER -