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Renin Angiotensin Aldosterone System Gene Polymorphisms among Type 2 Diabetic Patients with Retinopathy and
Vaishali S Pawar1, Kailas D Datkhile2, Ajit V Sontakke1
1Department of Biochemistry, Krishna Institute of Medical Sciences, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India.
Introduction:
Diversified pathways are associated with the advancement of type 2 diabetes mellitus (T2DM) towards retinopathy and nephropathy. Experimental data have suggested the role of renin-angiotensin-aldosterone system (RAAS) gene polymorphism in diabetic nephropathy (DN) patients. Since very few combined studies were done for RAAS genes in T2DM patients with DN and diabetic retinopathy (DR), we tried to explore the association of certain RAAS gene polymorphisms in them.
Methods:
Single nucleotide polymorphisms (SNPs), Met235Thr of angiotensinogen (AGT) gene, and insertion/deletion (ins/del) of angiotensin-converting enzyme (ACE) gene from RAAS pathway were studied using polymerase chain reaction (PCR) method in this cross-sectional study. T2DM patients diagnosed with nephropathy and retinopathy were selected (n = 125 each) consecutively and compared with T2DM patients without DN and/or DR. SPSS software was used for statistical analysis.
Results:
Considerably higher blood pressure, serum urea, and creatinine levels were found among DN patients. The DD genotype of ACE SNP was significantly higher in the DR and DN groups (OR: 2.87,95%CI: 1.48-5.56, P = 0.002 and OR: 2.36,95%CI: 1.23-4.53, P = 0.010) compared to the DM Group. In AGT Met235Thr SNP, the CC and TC genotypes were significantly increased in DN while only the TC genotype was significantly increased in the DR group.
Conclusion:
ACE ins/del and AGT Met235Thr SNPs were significantly related to the risk of development of nephropathy and retinopathy in T2DM patients.
Insights
Polymorphisms in renin-angiotensin-aldosterone system (RAAS) genes, specifically ACE and AGT, are linked to diabetic nephropathy and retinopathy in type 2 diabetes mellitus (T2DM) patients. These genetic variations increase the risk of developing these serious T2DM complications.
Area of Science:
- Genetics
- Endocrinology
- Nephrology
Background:
- Type 2 diabetes mellitus (T2DM) can lead to severe complications like diabetic nephropathy (DN) and diabetic retinopathy (DR).
- The renin-angiotensin-aldosterone system (RAAS) plays a role in blood pressure regulation and has been implicated in DN.
- Limited research exists on the combined association of RAAS gene polymorphisms with both DN and DR in T2DM patients.
Purpose of the Study:
- To investigate the association between specific RAAS gene polymorphisms and the development of DN and DR in T2DM patients.
- To explore the risk conferred by angiotensinogen (AGT) Met235Thr and angiotensin-converting enzyme (ACE) insertion/deletion (ins/del) polymorphisms.
Main Methods:
- A cross-sectional study involving 125 T2DM patients with DN and 125 with DR, compared to T2DM patients without these complications.
- Analysis of single nucleotide polymorphisms (SNPs) in the ACE (ins/del) and AGT (Met235Thr) genes using polymerase chain reaction (PCR).
- Statistical analysis performed using SPSS software to determine associations and odds ratios (OR).
Main Results:
- Patients with DN exhibited significantly higher blood pressure, serum urea, and creatinine levels.
- The DD genotype of the ACE SNP was significantly more prevalent in both DR and DN groups (OR: 2.87 and 2.36, respectively).
- The CC and TC genotypes of the AGT Met235Thr SNP were significantly increased in DN patients, while the TC genotype was increased in DR patients.
Conclusions:
- ACE ins/del and AGT Met235Thr gene polymorphisms are significantly associated with an increased risk of developing diabetic nephropathy and retinopathy in T2DM patients.
- These findings highlight the role of RAAS gene variations in the pathogenesis of T2DM-related microvascular complications.
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