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Published on: April 4, 2018
Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy
Anna Möllsten1, Maija Wessman, Maria Svensson
1Department of Clinical Sciences, Umeå University, Umeå, Sweden. anna.mollsten@pediatri.umu.se
Annals of Medicine
|November 15, 2006
Summary
The Glu/Glu genotype of the NOS3 Glu298Asp polymorphism is linked to a higher risk of diabetic nephropathy (DN) in type 1 diabetes patients. This genetic factor may independently increase DN risk, alongside other known factors like smoking and hypertension.
Area of Science:
- Genetics
- Nephrology
- Endocrinology
Background:
- Diabetic nephropathy (DN) risk correlates with intraglomerular pressure, potentially influenced by nitric oxide (NO).
- NO production is affected by endothelial NO-synthase gene (NOS3) polymorphisms, hyperglycemia, and smoking.
- Investigating NOS3 gene variations in Caucasian type 1 diabetes (T1D) patients is crucial for understanding DN etiology.
Purpose of the Study:
- To investigate the association between two NOS3 gene polymorphisms (Glu298Asp and NOS4ab) and the risk of developing DN in Caucasian T1D patients.
- To identify genetic predispositions that contribute to the development of DN.
Main Methods:
- A cross-sectional case-control study included 1510 Finnish and Swedish T1D patients.
- Incipient DN was defined by albumin excretion rate (AER) of 20-200 microg/min; overt DN by AER >200 microg/min or renal replacement therapy.
- Genetic markers analyzed were the NOS4ab 27 bp repeat and the Glu298Asp (rs1799983) polymorphism.
Main Results:
- Homozygosity for the Glu-allele of the Glu298Asp polymorphism was independently associated with an increased risk of DN (OR = 1.46).
- Smoking (OR = 2.13), male sex (OR = 1.61), HbA1c, and blood pressure also significantly increased DN risk.
- The NOS4 a-allele showed no association with DN risk.
Conclusions:
- The Glu/Glu genotype of the NOS3 Glu298Asp polymorphism may independently increase the risk of developing DN.
- This genetic association provides further insight into the multifactorial nature of diabetic nephropathy.
- Understanding these genetic factors can aid in personalized risk assessment and management strategies for T1D patients.
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