Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size

Akagawa, Hiroyuki; Kasuya, Hidetosiii; Onda, Hideaki; Yoneyama, Taku; Sasahara, Atsushi; Kim, Chul-Jin; Lee, Jung-Chung; Yang, Tae-Ki; Hori, Tomokatsu; Inoue, Ituro

doi:10.3171/jns.2005.102.1.0068

Cited by 28 publications

(26 citation statements)

References 10 publications

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“…32 In contrast, some recent studies on the polymorphism of eNOS have failed to demonstrate the positive relation with CA formation or rupture. 33 These results may suggest that the dysfunction of eNOS can be compensated for with nNOS upregulation in cerebral arteries unlike in the aorta and further strengthen the hypothesis that there is a functional difference in NOS regulation.…”

Section: Discussionsupporting

confidence: 64%

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

Aoki

Nakagawa

Kataoka

et al. 2011

Laboratory Investigation

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The rupture of cerebral aneurysm (CA) and subsequent subarachnoid hemorrhage can cause fatal results. Recent experimental findings have suggested that the mechanism of CA formation is based on chronic inflammation in arterial walls by hemodynamic force. Endothelial nitric oxide synthase (eNOS) protects arterial walls from vascular inflammation by relieving hemodynamic force through nitric oxide (NO) production. Thus, the expression and protective role of eNOS in CA formation have been investigated in this study. In this study, experimental induced rodent CA models by carotid ligation and systemic hypertension were used. The expression of eNOS was examined in rat CA models and revealed that it was decreased at the site of CA formation. Next, CA was induced in eNOS À/À mice to clarify the role of eNOS in CA formation. In eNOS À/À mice, the incidence of CA formation was similar to that found in wild-type mice. In CA walls of eNOS À/À mice, the expression of neuronal nitric oxide synthase (nNOS) was upregulated compared with that in wild-type mice, suggesting the compensatory effect of nNOS. Hence, eNOS À/À nNOS À/À mice were generated, underwent CA induction and confirmed that eNOS À/À nNOS À/À mice exhibited an increased incidence of CA formation accompanied by accelerated macrophage infiltration. These results suggested that the deficiency of eNOS could be compensated by nNOS upregulation in cerebral arteries and that the eNOS and nNOS complementarily had the protective role in CA formation. The results of this study will provide us with new insight about the mechanisms of CA formation and the functional redundancy between eNOS and nNOS in cerebral arteries.

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Section: Discussionsupporting

confidence: 64%

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

Aoki

Nakagawa

Kataoka

et al. 2011

Laboratory Investigation

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“…On the other hand, Krischek et al 19 reported no relationship between eNOS polymorphisms and rupture of a cerebral aneurysm in Japanese patients. Moreover, Akagawa et al 1 reported the same findings of negative association between the T786C polymorphism of the eNOS gene and the formation of an intracranial aneurysm.…”

Section: Discussionsupporting

confidence: 56%

“…The outcome was similar to the previously reported findings in control populations. 1,16 There were no racial differences in the eNOS gene polymorphism distributions in similar races, such as Korean and Japanese patients. However, there were racial differences in different races, such as Korean and American or Korean and German patients.…”

Section: Discussionmentioning

confidence: 99%

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The relationships between endothelial nitric oxide synthase polymorphisms and the formation of intracranial aneurysms in the Korean population

Kim

Baek

et al. 2011

FOC

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Object Some genetic factors are known to be associated with the formation of cerebral aneurysms in the Caucasian population. One of these factors is endothelial nitric oxide synthase (eNOS) gene polymorphisms. Endothelial nitric oxide synthase genes encode eNOS, which synthesizes NO from l-arginine. There continues to be controversy about the relationships between eNOS gene polymorphisms and the formation of intracranial aneurysms. In this study, the authors evaluated these relationships in the Korean population. Methods Three eNOS polymorphisms (eNOS 27VNTR, T786C, and G894T) were genotyped in 96 patients with ruptured aneurysms, 53 patients with unruptured aneurysms, and in 121 volunteers via polymerase chain reaction–restriction fragment length polymorphism analysis. Results The mean ages of the patients and healthy volunteers were 52.9 ± 12.3 years and 55.2 ± 9.1 years, respectively. The patient group was composed of 56 men and 93 women, and the healthy volunteer group was composed of 46 men and 75 women. Only the incidence of smoking history was significantly higher in the patient group than in the control group (p = 0.001). The genotypic frequencies for the 3 eNOS gene polymorphisms were in agreement with those predicted by Hardy-Weinberg equilibrium. There were no significant associations between the eNOS recessive models and the formation of an aneurysm. The authors found no genotypic differences between similar races among patients with aneurysms. Conclusions The present study shows that eNOS 27VNTR, T786C, and G894T polymorphisms cannot be used as indicators of the formation of intracranial aneurysms in Korean patients. To confirm these findings an additional analyses might need to be performed using a larger sample size. There were no differences in the genotypic distributions and allelic frequencies between similar races among patients with aneurysms, which were the same in previously reported normal populations.

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“…One study group concluded that a polymorphism of the eNOS gene correlates with the aneurysm's size, observed in Caucasian patients (Khurana et al 2003). But this could not be replicated in a study using DNA samples of Japanese patients (Akagawa et al 2005). It was also reported that three polymorphisms of this gene make it possible to single out patients with IAs that are more prone to rupture, comparing 58 ruptured to 49 unruptured IA cases of Caucasian origin (Khurana et al 2005).…”

Section: Candidate Gene Analysismentioning

confidence: 95%

The genetics of intracranial aneurysms

Krischek

Inoue

2006

J Hum Genet

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The rupture of an intracranial aneurysm (IA) leads to a subarachnoid hemorrhage, a sudden onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension and excessive alcohol intake are associated with subarachnoid hemorrhage. IAs, ruptured or unruptured, can be treated either surgically via a craniotomy (through an opening in the skull) or endovascularly by placing coils through a catheter in the femoral artery. Even though the etiology of IA formation is mostly unknown, several studies support a certain role of genetic factors. In reports so far, genome-wide linkage studies suggest several susceptibility loci that may contain one or more predisposing genes. Studies of several candidate genes report association with IAs. To date, no single gene has been identified as responsible for IA formation or rupture. The identification of susceptible genes may lead to the understanding of the mechanism of formation and rupture and possibly lead to the development of a pharmacological therapy.

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Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size

Abstract: The eNOS T-786C SNP genotype does not influence the size of aneurysms.

Cited by 28 publications

References 10 publications

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

The relationships between endothelial nitric oxide synthase polymorphisms and the formation of intracranial aneurysms in the Korean population

The genetics of intracranial aneurysms

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