Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

Abstract

Object. The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3).Methods. Three hundred thirty-three Caucasian SAH patients and 498 controls were genotyped for the -922A > G (rs 1800779), -786T > C (rs2070744), and 894G > T (rs1799983) single nucleotide polymorphisms and the intron-4 27-bp variable number of tandem repeats polymorphism (27-bp-VNTR).Results. The b/b (5 repeats) genotype of the 27-bp-VNTR was overrepresented in cases (77%) versus controls (69%) (p = 0.02). In male patients the b/b genotype was found in 85% compared with 67% in male controls, whereas in women, the frequencies were 73% and 72%, respectively. This corresponds to an odds ratio of 2.8 (95% CI 1.5-5.6, p = 0.0005) for SAH in men with the b/b genotype versus men with a/b or a/a. In women, no such association was found (OR 1.1, 95% CI 0.7-1.6, p = 0.76). Stepwise logistic regression including arterial hypertension, smoking, sex, and age with interactions yielded similar effect estimates of the 27-bp-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect.Conclusions. The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH. This effect is not mediated by any single NOS3 haplotype.

Epigenetic response of endothelial cells to different wall shear stress magnitudes: A report of new mechano‐miRNAs

“…At a critical stage, when the flow in the aneurysm changes from the growth‐promoting HWSS status to more pathologic flows with transition to turbulence or very low WSS (Saqr et al, ), the epigenetic and transcriptional network in ECs shifts to a death promoting cascade that leads to ECs shedding and exposure of the aneurysmal wall promoting rupture, as observed previously (Cebral et al, ; Saqr et al, ). A disruption in the protective gene network during aneurysm growth, such as the observed NOS3 polymorphism (Staalso et al, ) may lead to accelerated rupture of aneurysms.…”

Association Between Three eNOS Polymorphisms and Intracranial Aneurysms Risk

“…Furthermore, sensitivity analysis was performed to evaluate the stability of the results by excluding 1 single study at a time. The overall association between T786C polymorphism and IA risk was significantly influenced by the study of Staalsø et al 34 When excluding the study by Staalsø et al, an increased risk of significance was associated with T786C polymorphism in heterozygous comparison of codominant model (OR = 1.266, 95% CI = 1.050–1.526) and dominant model (OR = 1.255, 95% CI = 1.049–1.503) (Figures 4 and 5 ). The pooled ORs and corresponding 95% CIs were not significantly altered when any individual study was excluded for the other models of T786C and all models of G894T and 27-bp-VNTR polymorphisms (data not shown).…”

“… 18 Khurana et al 24 first investigated the relationship between the T786C polymorphism and IA susceptibility and no significant association was found. After that, 9 studies from 8 articles had been done, 26 – 30 , 32 – 34 and the result of 5 studies was negative. 27 , 30 , 32 – 34 The other 4 Asian studies have analyzed genotype of cases and controls but did not conclude the association.…”

“…After that, 9 studies from 8 articles had been done, 26 – 30 , 32 – 34 and the result of 5 studies was negative. 27 , 30 , 32 – 34 The other 4 Asian studies have analyzed genotype of cases and controls but did not conclude the association. 26 , 28 , 29 For G894T, 3 of 9 studies showed significant associations with IA risk, 31 , 33 , 35 and the other 6 got inverse result.…”

“… 26 , 28 , 29 For G894T, 3 of 9 studies showed significant associations with IA risk, 31 , 33 , 35 and the other 6 got inverse result. 25 , 27 , 28 , 30 , 32 , 34 Seven studies investigated 27-bp-VNTR and the risk of IA, and significant association was found in 3 of them, 25 , 34 , 36 but was not found in the remaining 4. 27 , 28 , 30 , 32 …”