The presence of the 1068 G>A variant of P2X7 receptors is associated to an increase in IL-1Ra levels, insulin secretion and pancreatic β-cell function but not with glycemic control in type 2 diabetes patients
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It has been reported that an increased function of the P2X7 purinergic receptor is associated with an increase in both insulin sensitivity and secretion. Accordingly, we explored the possible effect of the 1068 G>A polymorphism of the gene P2RX7 on glucose homeostasis and the levels of the anti-inflammatory cytokine IL-1Ra in T2D patients. The presence of the 1068 G>A polymorphism in T2D patients (n = 100) and healthy subjects (n = 100) was determined by DNA sequencing, and serum levels of IL-1Ra were measured by ELISA. Pancreatic β-cell function, insulin resistance, blood glucose levels and glycated hemoglobin (HbA1c) were also analyzed. We detected a significant negative association between T2D and the 1068 G>A SNP (Odds ratio 0.3916, p = 0.0045). In addition, we observed that T2D patients bearing the 1068 G>A variant showed higher serum levels of IL-1Ra compared to both, patients with the GG genotype or healthy individuals (GG or G>A). Moreover, T2D patients bearing the 1068 G>A SNP showed increased insulin levels and a better pancreatic β-cell function (p < 0.05 in both cases) compared to patients with the wild type genotype. However, the HbA1c levels, fasting glucose levels and the degree of insulin resistance were similar in T2D patients carrying or not the G>A SNP. Our results suggest that although the 1068 G>A polymorphism of the P2RX7 gene is associated with an increased β-cell function and IL-1Ra release in T2D patients, the glycemic control is not significantly affected by the presence of this SNP. © 2018 Elsevier B.V.
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HOMA-B; IL-1Ra; P2X7 receptor; Polymorphism; Type 2 diabetes hemoglobin A1c; interleukin 1 receptor blocking agent; purinergic P2X7 receptor; glycosylated hemoglobin; hemoglobin A1c protein, human; insulin; interleukin 1 receptor blocking agent; purinergic P2X7 receptor; adult; amplicon; Article; cell function; controlled study; diabetic patient; DNA sequence; enzyme linked immunosorbent assay; female; gene; genetic polymorphism; glucose blood level; glucose homeostasis; glycemic control; human; insulin release; insulin resistance; insulin sensitivity; major clinical study; male; non insulin dependent diabetes mellitus; P2RX7 gene; pancreas islet beta cell; polymerase chain reaction; priority journal; protein blood level; protein function; single nucleotide polymorphism; blood; case control study; gene expression; genetics; genotype; metabolism; middle aged; non insulin dependent diabetes mellitus; pancreas islet beta cell; pathology; secretion (process); single nucleotide polymorphism; Adult; Blood Glucose; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Gene Expression; Genotype; Glycated Hemoglobin A; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Interleukin 1 Receptor Antagonist Protein; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Purinergic P2X7
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