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Nitric oxide synthase gene polymorphisms and diabetic nephropathy
J D Rippin1, A Patel, N D Belyaev
1Division of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Undergraduate Centre, Bordeley Green East, Birmingham B9 5SS, United Kingdom. J.D.RIPPIN@bham.ac.uk
Diabetologia
|April 11, 2003
Summary
Genetic variations in nitric oxide synthase genes (NOS3 and NOS2A) were not associated with diabetic nephropathy in Type 1 diabetes patients. This study found no link between these specific gene polymorphisms and the development of kidney disease in this population.
Area of Science:
- Genetics
- Nephrology
- Endocrinology
Background:
- Diabetic nephropathy (DN) in Type 1 diabetes (T1D) is largely genetically influenced, with significant cardiovascular risk concentrated in affected patients.
- Endothelial dysfunction, a hallmark of cardiovascular disease, is linked to hypertension, dyslipidaemia, and smoking, all associated with DN.
- Nitric oxide (NO) regulates endothelial function, making genes encoding NO synthases (NOS) potential candidates for conferring DN susceptibility.
Purpose of the Study:
- To investigate the association between polymorphisms in NOS3 (endothelial NO synthase) and NOS2A (inducible NO synthase) genes and the susceptibility to diabetic nephropathy in Type 1 diabetes.
- To validate or refute previous findings suggesting a role for NOS3 intron 4 polymorphism in DN.
Main Methods:
- A case-control study involving Caucasian patients with Type 1 diabetes and overt nephropathy (cases) and long-standing Type 1 diabetes patients with minimal nephropathy risk (controls).
- Genotyping of NOS3 intron 4 and NOS2A promoter polymorphisms was performed using polymerase chain reaction (PCR) and gel electrophoresis techniques.
Main Results:
- No significant association was found between NOS3 intron 4 genotypes (aa, ab, bb) and diabetic nephropathy (p=0.935) in 860 subjects.
- No significant association was observed between NOS2A promoter genotypes (+/+, +/-, -/-) and diabetic nephropathy (p=0.952) in 715 subjects.
Conclusions:
- The studied polymorphisms in NOS3 and NOS2A genes are not associated with diabetic nephropathy in this cohort of Caucasian Type 1 diabetes subjects.
- Previous suggestions of a role for NOS3 intron 4 polymorphism in DN susceptibility are not confirmed by this larger study.