NOS3 gene

The NOS3 gene (NOS3 stands for Nitric Oxide Synthase 3) is a protein-coding gene located on chromosome 7q36.1. An important paralog of this gene is NOS1. Alternative splicing and the use of alternative promoters lead to several transcript variants.

The protein encoded by the NOS3 gene is endothelial nitric oxide synthase (eNOS). Together with inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), it catalyzes the formation of nitric oxide and L-citrulline from L-arginine and molecular oxygen. eNOS is activated at calcium concentrations above 100 nM. Nitric oxide (NO) is involved in vascular smooth muscle relaxation via a cGMP-mediated signal transduction pathway (Janssens SP et al. 1992).

Nitric oxide is a reactive free radical that acts as a biological mediator in several processes, including neurotransmission and antimicrobial and antitumor activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary arteries and promotes blood clotting by activating platelets. Reports of single nucleotide polymorphisms in the NOS3 gene in patients with atopic dermatitis (Svitich ОА et al. 2021) require further verification with regard to their sustainability.

NO synthase is involved in many physiological and pathological processes and catalyzes the oxidation of L-arginine to L-citrulline with NO release. NO synthase has three isoforms: inducible (iNOS) and two constitutive neuronal (nNOS) and endothelial (eNOS). The activity of different isoforms of NO synthase has a direct effect on the NO concentration, which in turn influences the immune and repair processes and thus the course of the disease. There is evidence that eNOS is involved in various pathological processes. The importance of the enzyme has been demonstrated at the molecular and genetic level.

Diseases associated with NOS3 include stroke, ischemic and Alzheimer's disease, familial, 1.

1. Janssens SP et al. (1992) Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 267:14519-14522.
2. Svitich ОА et al. (2021) Association of the NOS3 Gene Polymorphisms with the Risk of Atopic Dermatitis in Children. Bull Exp Biol Med 170:787-790.
3. Zhou TB et al. (2013) Association of endothelial nitric oxide synthase Glu298Asp gene polymorphism with the risk of endstage renal disease. Ren Fail 35:573-578.