مختصر البحث:
The progressive metabolic condition known as type 2 diabetes mellitus (T2DM) is
characterized by chronic hyperglycemia, primarily due to insulin resistance and declining
pancreatic β-cell efficiency. It represents a major global health burden and …
The progressive metabolic condition known as type 2 diabetes mellitus (T2DM) is
characterized by chronic hyperglycemia, primarily due to insulin resistance and declining
pancreatic β-cell efficiency. It represents a major global health burden and is often
accompanied by long-term complications involving the cardiovascular, renal, and nervous
systems. Both environmental exposures and genetic susceptibilities play crucial roles in its
pathogenesis. One gene of interest, Hepatocyte Nuclear Factor 4 Alpha (HNF4A), encodes a
transcription factor that contributes to metabolic regulation and inflammatory signaling by
modulating acute-phase protein expression. Additionally, Interleukin-41 (IL-41), a recently
characterized cytokine, has been implicated in the interface between immune function and
metabolic control, gaining attention for its potential relevance in chronic diseases such as
T2DM.
The study aims at attaining the following: Evaluating the impact of HNF4A gene SNPs
(rs4810424 G/C and rs2144908 G/A) on T2DM patients and healthy controls that lead to find
the relationship between genetic regulation and metabolic dysfunction in type 2 diabetes.
Also measuring the expression levels of HNF4A protein in patients and healthy controls, and
explore the role of IL-41 in inflammation and metabolic control and its potential contribution
to metabolic regulation of T2DM.
A case-control study design was implemented, including 200 participants, group of 100
patients diagnosed with T2DM and another group of 100 persons of healthy controls, the age
and sex were matched between the groups. All participants had their anthropometric
measurements been taken, as well as and their fasting venous blood samples, also biochemical
evaluations included fasting glucose, insulin, lipid profiles, and inflammatory markers.
Genotypic analysis of HNF4A rs4810424G/C was carried out using the Restriction
Fragment Length Polymorphism(RFLP-PCR) technique with custom-designed primers. Real
Time-PCR(RT-PCR) was employed for rs2144908 G/A genotypic verification and expression
analysis. Associations of these two SNPs between genotype variants and biochemical indices
were analyzed using dominant, codominant, overdominant, recessive, and additive models.
Participants with T2DM showed significantly higher fasting blood glucose alongside elevated
insulin levels and increased HOMA-IR values. Lipid profile assessments revealed notable
increases in total cholesterol, triglycerides, LDL and VLDL levels among diabetics, with HDL
levels slightly reduced.
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