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Letter to the Editor. Influence of rare RNF213 variants other than p.R4810K on the clinical outcomes of moyamoya disease

Shunsuke Nomura, Akitsugu Kawashima, Hiroyuki Akagawa, and Takakazu Kawamata

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Using endothelial nitric oxide synthase gene polymorphisms to identify intracranial aneurysms more prone to rupture in Japanese patients

Boris Krischek, Hidetoshi Kasuya, Hiroyuki Akagawa, Atsushi Tajima, Akira Narita, Hideaki Onda, Tomokatsu Hori, and Ituro Inoue


Recent investigators found that the presence of three tandem polymorphisms of the endothelial nitric oxide synthase (eNOS) gene—promoter single nucleotide polymorphism (SNP) T-786C, intron-4 27-bp variable number of tandem repeats, and the G894T SNP in exon 7—was indicative of intracranial aneurysms more prone to rupture in a Caucasian patient sample. In the present study, the authors sought to determine whether the presence of these eNOS polymorphisms could indicate which Japanese patients with aneurysms were more endangered by a subarachnoid hemorrhage (SAH).


The three eNOSpolymorphisms were genotyped in 297 patients with ruptured aneurysms (RAs), 108 patients with unruptured aneurysms (UAs), and 176 healthy volunteers by using polymerase chain reaction.

The distribution of the variant alleles did not differ significantly (p > 0.05) between the RA group and the UA group. The frequency of the corresponding genotypes between the two groups and a haplotype analysis did not show any significant differences. Further comparisons of the RA and UA groups with the control group did not yield any significant allele or genotype frequency differences.


These data show that the examined set of eNOS polymorphisms were not indicative of which Japanese patients with intracranial aneurysms would suffer an SAH. The presence of eNOS polymorphisms is not useful in identifying intracranial aneurysms that are more prone to rupture in a Japanese patient sample.

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

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

Object. Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations—Japanese and Korean.

Methods. The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with IAs and 214 Japanese and 191 Korean control volunteers. Differences in genotype frequencies among the various aneurysm sizes were evaluated using the Fisher exact test.

There was no significant difference in heterozygous (T/C) eNOS T-786C SNP between aneurysms 5 mm or smaller and those from 6 to 9 mm, and between lesions 5 mm or smaller and those 10 mm or larger in 336 Japanese patients harboring aneurysms—220 with ruptured and 116 with unruptured lesions—and in 191 Korean patients with ruptured aneurysms.

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