CLINICAL IMMUNOLOGY
Reduced GLP-1 response to a meal is associated with the CTLA4 rs3087243 G/G genotype
1
2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
2
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
3
MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
4
Department of Probability Theory and Statistics, Eötvös Lóránd University, Budapest, Hungary
Submission date: 2017-02-04
Final revision date: 2017-05-19
Acceptance date: 2017-05-22
Publication date: 2019-09-30
Cent Eur J Immunol 2019;44(3):299-306
KEYWORDS
type 1 diabetesGLP-1autoimmuneCTLA4incretin responsegeneticassociation studySNPsgenetic susceptibility
ABSTRACT
Although insulitis is the characteristic main feature of type 1 diabetes mellitus (T1DM), many aspects of β cell loss still remain elusive. Immune dysregulation and alterations in the dipeptidyl-peptidase-4-incretin system might have a role in disease development, but their connection is poorly understood. We assessed the associations of a few selected, immunologically relevant single nucleotide gene variants with the DPP-4-incretin system in individuals with T1DM and in healthy controls. Prandial plasma (total, active) GLP-1 levels, serum DPP-4 activity, CD25 and CTLA-4 expression of T cells and DPP4 rs6741949, CTLA4 rs3087243, CD25 rs61839660 and PTPN2 rs2476601 SNPs were assessed in 33 T1DM patients and 34 age-, gender-, BMI-matched non-diabetic controls without a family history of T1DM. CTLA-4 expression was lower in the Foxp3+CD25+ regulatory T cells from individuals homozygous for the CTLA4 rs3087243-G variant compared to those who carry an A allele. Prandial plasma total GLP-1 levels 45 min after a standardized meal were reduced in individuals homozygous for the CTLA4 rs3087243 G major allele compared to A allele carriers both in the entire study population (with statistical power over 90%) and within the T1DM group. Here we report for the first time a reduced total prandial GLP-1 plasma concentration in individuals with the CTLA4 rs3087243 G/G genotype. One may speculate that immune response-related L cell damage might possibly explain this novel association.
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