Reduced GLP-1 response to a meal is associated with the CTLA4 rs3087243 G/G genotype

András Zóka; Gábor Barna; Gábor Nyírő; Ágnes Molnár; László Németh; Györgyi Műzes; Anikó Somogyi; Gábor Firneisz

doi:10.5114/ceji.2019.89604

eISSN: 1644-4124
ISSN: 1426-3912

Central European Journal of Immunology

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3/2019
vol. 44

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abstract:

Clinical immunology

Reduced GLP-1 response to a meal is associated with the CTLA4 rs3087243 G/G genotype

András Zóka

¹

,

Gábor Barna

²

,

Gábor Nyírő

³

,

Ágnes Molnár

¹

,

László Németh

⁴

,

Györgyi Műzes

¹

,

Anikó Somogyi

¹

,

Gábor Firneisz

^{1, 3}

2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
MTA-SE Molecular Medicine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary
Department of Probability Theory and Statistics, Eötvös Lóránd University, Budapest, Hungary

(Centr Eur J Immunol 2019; 44 (3): 299-306)

DOI: https://doi.org/10.5114/ceji.2019.89604

Online publish date: 2019/09/30

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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.

keywords:

Reduced GLP-1 response to a meal is associated with the CTLA4 rs3087243 G/G genotype

András Zóka 1 , Gábor Barna 2 , Gábor Nyírő 3 , Ágnes Molnár 1 , László Németh 4 , Györgyi Műzes 1 , Anikó Somogyi 1 , Gábor Firneisz 1, 3

type 1 diabetes, GLP-1, autoimmune, CTLA4, incretin response, genetic, association study, SNPs, genetic susceptibility

András Zóka

¹

,

Gábor Barna

²

,

Gábor Nyírő

³

,

Ágnes Molnár

¹

,

László Németh

⁴

,

Györgyi Műzes

¹

,

Anikó Somogyi

¹

,

Gábor Firneisz

^{1, 3}