Association Between Three eNOS Polymorphisms and Intracranial Aneurysms Risk

Abstract

Endothelial nitric oxide synthase (eNOS) is the catalyst of endothelial nitric oxide (NO) synthesis. Polymorphisms in the eNOS gene may influence the risk of intracranial aneurysm (IA), but the results of existing researches are still inconsistent. Thus, we performed the present meta-analysis to derive a more precise estimation between eNOS polymorphisms (T786C, G894T, 27-bp-variable number of tandem repeat [VNTR]) and IA risk.Case–control studies evaluating the association between the eNOS polymorphisms and IA risk were searched in PubMed, Ovid & Embase, Web of Science, and Chinese Wanfang datasets with the last search up to July 15, 2014. The pooled odds ratios (ORs) for the association between eNOS polymorphisms and IA and their corresponding 95% confidence intervals (CIs) were estimated using the random or fixed-effects model.Finally, 10 studies for T786C polymorphism (1819 cases and 1893 controls), 9 studies for G894T polymorphism (1393 cases and 1508 controls), and 7 studies for 27-bp-VNTR polymorphism (1281 cases and 1406 controls) were included in the meta-analyses. In the overall analysis, no evidence of association between eNOS polymorphisms and susceptibility of IA was found. When subgrouped by race descent, significantly increased risk was detected among Asians for T786C polymorphism (heterozygous comparison of codominant model: OR = 1.294, 95% CI = 1.025–1.634; dominant model: OR = 1.277, 95% CI = 1.019–1.600), but not in Caucasians or the other 2 polymorphisms.Our meta-analysis suggested that T786C polymorphism was associated with increased risk of IA among Asians, whereas G894T and 27-bp-VNTR polymorphisms might have no influence on the susceptibility of IA.

Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans

“…Endothelial cells express eNOS to serve as an important source of NO, a potent vasodilator and inhibitor of inflammation, platelet aggregation, and smooth muscle cell proliferation [ 42 ]. Interestingly, eNOS gene polymorphisms have been associated with vascular diseases [ 43 ]; two recent meta-analyses have identified the T786C polymorphism of eNOS as a predictor for the development of intracranial aneurysms in the cerebral vascular system [ 44 , 45 ], and various polymorphisms of eNOS have been linked to AAA [ 46 – 48 ]. Our findings of increased eNOS levels in larger aneurysms are in accordance with a recent animal study [ 49 ], in which increased eNOS activity reduced smooth muscle α-actin and upregulated MMPs during flow-induced intracranial aneurysm formation.…”

Late onset MELAS with m.3243A > G mutation and its association with aneurysm formation

“…First, regarding endothelial dysfunction, nitric oxide (NO) synthesis by endothelial nitric oxide synthase (eNOS) was decreased. Second, asymmetric dimethylarginine, an NOS (Yang et al 2015) revealed an association between eNOS and intracranial aneurysm (IA) risk. The study suggested that T786C polymorphisms are associated with the susceptibility to IA in the Asian population; however, G894T and 27-bp-VNTR likely have no influence on this condition.…”

The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage

“…NOS‐3 knockout predisposed mice subjected to unilateral carotid artery ligation to the formation of intracranial aneurysms (Abruzzo et al ., ). Single nucleotide polymorphisms (SNPs) in the eNOS gene are associated with the risk of developing IA in several populations (Yang et al ., ; Paschoal et al ., ).…”