Impact of the serum epidermal growth factor polymorphism rs4444903 and gene expression in PBMCs on glycemic control in type 2 diabetes mellitus
Keywords:
EGF, rs4444903 SNP, glycemic control, gene expression, peripheral blood mononuclear cells, diabetes mellitus type 2 (T2DM), case-control studyAbstract
Background: Poor glycemic control is a major concern in type 2 diabetes mellitus (T2DM) patients and is associated with a higher risk of complications and increased mortality. The role of EGF in maintaining pancreatic beta cells is well-established, however, there is a lack of evidence regarding the association between EGF and glycemic control. This study aimed to investigate the association between rs4444903 polymorphism of the EGF gene, EGF gene expression, and EGF levels with T2DM.
Methods: This was a two-phase case-control study. The first phase included 330 patients with good or poor glycemic control (1:1 ratio). The second phase included 42 patients per group. Serum EGF protein was measured using ELISA. EGF rs4444903 genotype was determined using PCR-RFLP. EGF mRNA in PBMCs was quantified using RT-qPCR.
Results: Poor glycemic control was associated with lower serum EGF levels. GA genotype of rs4444903 was more frequent among the poor control group (P<0.05). Regression analysis demonstrated that EGF lowered the risk of poor glycemic control (OR=0.99, 95%CI:0.98-0.99, P<0.001) and GA genotype was associated with a two-fold increase in poor control risk (OR=1.96, 95%CI:1.02-3.57, P=0.04). Poor control patients had a 40% reduction in EGF mRNA in their PBMCs (P<0.05). Lower EGF expression was associated with poor glycemic control (OR=3.05, 95%CI:1.10-8.44, P=0.03).
Conclusions: This study provides evidence that low serum EGF levels, decreased EGF mRNA in PBMCs, and the GA genotype of the rs4444903 are associated with poor glycemic control in T2DM. Further research is warranted to investigate the clinical implications/applications of this association.
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