Association of polymorphisms of endothelial nitric oxide synthase (eNOS) gene with the risk of primary open angle glaucoma in a Brazilian population

Vascular and autonomic dysregulation in primary open-angle glaucoma

“…One study found no difference in two functional NOS3 gene variants (the gene coding for the enzyme responsible for NO generated by vascular endothelium) between HTG and NTG cases. 15 On the other hand, several other research group 16–23 have found associations between functional NOS3 gene variants and POAG cases versus controls. In fact, three studies find that the -786C/T NOS3 locus is associated with HTG, particularly in women (Table 1).…”

“…This is in contrast to the evidence of replication for associations between a functional variant in the NOS3 promoter region (−786C), which is adversely associated with HTG in women. 16,22,23 and between CAV1/CAV2 variants and POAG. 43,44 …”

“…In fact, three studies find that the -786C/T NOS3 locus is associated with HTG, particularly in women (Table 1). 16,22,23 Interestingly, the -786 C/T NOS3 polymorphism is a function variant that results in reduced nitric oxide levels in cells because of alterations in NOS3 transcription rates. 24 In addition, polymorphisms in the genomic region corresponding to the caveolin genes, which code for proteins that reciprocally control NOS3 activity in endothelial endocytotic membranes, 25 are also associated with POAG.…”

Regulation of intraocular pressure by soluble and membrane guanylate cyclases and their role in glaucoma

“…Also, NADPH-diaphorase (NADPH-d) reactivity, a marker for NO production, was decreased in TM, SC, and anterior longitudinal CM fibers isolated from POAG eyes (Nathanson and Mckee, 1995a) and serum levels of L-arginine analogs (endogenous NOS inhibitors) were found to be elevated in patients with advanced glaucoma (Javadiyan et al, 2012). In addition, NOS3 gene variants were associated with POAG in women (see “Genetics of POAG” below Kang et al, 2010; Magalhaes Da Silva et al, 2012). Together, these studies suggest that impaired NO-cGMP signaling can contribute to the etiology of POAG, identifying the NO-cGMP signaling pathway as a potential therapeutic target for POAG.…”

“…Second, A candidate gene association study in 527 incident cases and 1543 controls revealed interactions between NOS3 gene variants, potentially affecting expression and/or activity of NOS3, and high tension POAG in females (Kang et al, 2010). In addition, a functional NOS3 polymorphism (T-786C) was associated with POAG and appears to interact with gender and age in modulating the risk of POAG (Magalhaes Da Silva et al, 2012). The same variant also affects the interaction of systemic hypertension and cigarette smoking with POAG risk, highlighting the complex gene-environment interactions that impact the etiology of POAG (Kang et al, 2011).…”