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Gene Expression Analysis in T2DM and Its Associated Microvascular Diabetic Complications: Focus on Risk Factor and
Laxmipriya Jena1, Prabhsimran Kaur1, Tashvinder Singh1
1Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, 151401, India.
Abstract:
Prolonged hyperglycemic conditions in type 2 diabetes mellitus (T2DM) cause pathological and functional damage to many organs and tissues, including the kidneys, retina, skin, and neuronal tissues, resulting in the development of microvascular diabetic complications. The altered renin angiotensin aldosterone system (RAAS) pathway has been reported to play an important role in the development of insulin resistance in T2DM and associated complications. The current study was carried out to evaluate the association of risk factors and altered expression of RAAS genes in T2DM patients without complications and T2DM patients with complications (retinopathy, nephropathy, and neuropathy). Four hundred and twenty subjects including 140 healthy controls, 140 T2DM patients with diabetic complications, and 140 T2DM patients without diabetic complications were included in the study. Risk factors associated with the development of T2DM and diabetic complications were evaluated. Further, expression analysis of RAAS genes (AGT, ACE, ACE2, and AGT1R) was carried out using qRTPCR in healthy controls, T2DM patients with complications, and T2DM patients without complications. Various risk factors like urban background, higher BMI, alcoholism, smoking, and family history of diabetes among others were found to be associated with the development of T2DM as well as diabetic complications. The expression level of AGT, ACE, and AGT1R was found to be upregulated whereas ACE2 was found to be downregulated in T2DM patients with complications and T2DM patients without complications as compared to controls. Altered expression of the studied genes of RAAS pathway is associated with the development of microvascular diabetic complications.
Insights
Type 2 diabetes mellitus (T2DM) complications are linked to altered expression of renin angiotensin aldosterone system (RAAS) genes. Risk factors like higher BMI and smoking also contribute to T2DM and its microvascular complications.
Area of Science:
- Endocrinology and Metabolism
- Genetics and Molecular Biology
Background:
- Prolonged hyperglycemia in type 2 diabetes mellitus (T2DM) leads to microvascular complications affecting kidneys, retina, and nerves.
- The renin-angiotensin-aldosterone system (RAAS) is implicated in insulin resistance and T2DM-related complications.
Purpose of the Study:
- To investigate the association between risk factors and RAAS gene expression in T2DM patients.
- To compare RAAS gene expression in T2DM patients with and without diabetic complications versus healthy controls.
Main Methods:
- Cross-sectional study involving 420 subjects: 140 healthy controls, 140 T2DM patients with complications, and 140 T2DM patients without complications.
- Evaluation of risk factors for T2DM and its complications.
- Quantitative real-time PCR (qRTPCR) to analyze the expression of RAAS genes (AGT, ACE, ACE2, AGT1R).
Main Results:
- Identified risk factors for T2DM and complications include urban living, high BMI, alcoholism, smoking, and family history.
- Upregulation of AGT, ACE, and AGT1R gene expression observed in T2DM patients (with and without complications) compared to controls.
- Downregulation of ACE2 gene expression found in T2DM patients (with and without complications) compared to controls.
Conclusions:
- Altered expression of RAAS pathway genes is associated with the development of microvascular diabetic complications in T2DM.
- Specific RAAS gene expression patterns may serve as indicators or contributors to diabetic complications.
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