Chloroplast translation factor EF-Tu of Arabidopsis thaliana can be inactivated via oxidation of a specific cysteine residue.

Translational elongation factor EF-Tu, which delivers aminoacyl-tRNA to the ribosome, is susceptible to inactivation by reactive oxygen species (ROS) in the cyanobacterium Synechocystis sp. PCC 6803. However, the sensitivity to ROS of chloroplast-localized EF-Tu (cpEF-Tu) of plants remains to be elucidated. In the present study, we generated a recombinant cpEF-Tu protein of Arabidopsis thaliana and examined its sensitivity to ROS in vitro. In cpEF-Tu that lacked a bound nucleotide, one of the two cysteine residues, Cys149 and Cys451, in the mature protein was sensitive to oxidation by H2O2, with the resultant formation of sulfenic acid. The translational activity of cpEF-Tu, as determined with an in vitro translation system, derived from Escherichia coli, that had been reconstituted without EF-Tu, decreased with the oxidation of a cysteine residue. Replacement of Cys149 with an alanine residue rendered cpEF-Tu insensitive to inactivation by H2O2, indicating that Cys149 might be the target of oxidation. In contrast, cpEF-Tu that had bound either GDP or GTP was less sensitive to oxidation by H2O2 than nucleotide-free cpEF-Tu. The addition of thioredoxin f1, a major thioredoxin in the Arabidopsis chloroplast, to oxidized cpEF-Tu allowed the reduction of Cys149 and the reactivation of cpEF-Tu, suggesting that the oxidation of cpEF-Tu might be a reversible regulatory mechanism that suppresses the chloroplast translation system in a redox-dependent manner.

Optimal timing and safety of the external ventricular drainage in patients with high-grade aneurysmal subarachnoid hemorrhage treated with endovascular coiling.

The presented retrospective analysis has evaluated the optimal timing and safety of external ventricular drainage (EVD) for acute hydrocephalus after aneurysmal subarachnoid hemorrhage (aSAH). The study cohort comprised 102 patients, 49 of whom underwent EVD at 3-120 h (mean, 16 h) after the clinical onset of aSAH, either before (N = 27) or after (N = 22) ruptured aneurysm coiling. Among those treated with EVD, favorable and fair outcomes at discharge (modified Rankin Scale [mRS] scores 0-3) were noted in 14 (29%) and unfavorable (mRS scores 4-6) in 35 (71%). The former was more common among women (P = 0.019) and patients without chronic arterial hypertension (P = 0.028). The cut-off value for optimal timing of EVD was defined at 13 h after the onset of aSAH. Favorable and fair outcomes were more frequent after early (≤13 h; N = 30) than late (>13 h; N = 19) EVD (40% vs. 11%; P = 0.026), whereas did not differ significantly between those in whom such procedure was done before or after ruptured aneurysm coiling (19% vs. 41%; P = 0.083). In the entire study cohort, 2 patients had re-rupture of the aneurysm, and while both of them were treated with EVD, neither case of complication was directly associated with the procedure and, in fact, preceded it. In conclusion, EVD for management of acute hydrocephalus in patients with high-grade aSAH should be preferably applied within 13 h after the clinical onset of stroke, which may be considered sufficiently safe regardless whether it is performed before or after ruptured aneurysm coiling.

A case of idiopathic extracranial carotid artery pseudoaneurysm with a rare clinical course and pathological features.

Extracranial carotid artery aneurysms (ECAAs) are rare, with the etiology mainly classified as degeneration or dissection. Pseudoaneurysms in the region are even rarer and are seen following trauma, iatrogenic injury, or infection. We report a case of extracranial carotid artery pseudoaneurysm (pseudo-ECAA) with a rare clinical course and pathological features. A 58-year-old man presented with swelling and purpura on the left side of his neck after sneezing. Radiological examinations suggested a ruptured left common carotid artery aneurysm. The operative findings were consistent with a pseudoaneurysm. Pathological examination revealed disarrangement and degeneration of smooth muscle fibers in the media, in addition to scattered foci of mucoid accumulation and irregular-shaped cavitation in the medial extracellular matrix, raising the possibility of an intrinsic dysfunction of the vascular wall in the pathological process of pseudoaneurysm formation.

[A Case of Segmental Arterial Mediolysis:Subarachnoid Hemorrhage Followed by Abdominal Bleeding].

We describe a case involving subarachnoid and intraperitoneal hemorrhage due to segmental arterial mediolysis(SAM). A 77-year-old female patient with sudden subarachnoid hemorrhage was immediately transferred to our institution. The hemorrhage was classified as grade 2 according to the World Federation of Neurosurgical Societies system. The patient was a non-smoker and did not drink alcohol regularly. A right internal carotid aneurysm was detected using CT angiography and was clipped during frontotemporal craniotomy. Bleeding was observed from the anterior wall of the internal carotid artery, and the tear was clipped. The patient had an uneventful postoperative course until sudden cardiopulmonary arrest eight days after craniotomy. She died of massive intraperitoneal hemorrhage. Autopsy revealed that the hemorrhage was due to dissection of the celiac artery. Tunica media denaturation was observed not only in the celiac artery, but also in the splenic and internal carotid arteries, which exhibited ruptured aneurysms, and the patient was diagnosed with segmental arterial mediolysis(SAM). SAM is an arterial degenerative disease affecting the medial layer of the arterial and dissecting walls. Multiple lesions are sometimes found. Radiographic imaging findings of SAM are similar to those of dissecting aneurysms, which are characterized by a single continuous dissection of the medial layer. As observed in this case, abdominal bleeding caused by SAM can occur after intracranial bleeding. When surgeons encounter unusual intracranial dissecting aneurysms, SAM should be considered as a differential diagnosis.

Novel and recurrent RNF213 variants in Japanese pediatric patients with moyamoya disease.

Moyamoya disease is a progressive steno-occlusive condition of the main intracranial arteries that results in the compensatory formation of fragile moyamoya vessels at the base of the brain. RNF213 is the most significant susceptibility gene and is often found with the p.Arg4810Lys founder variant in East Asian patients. We identified three putatively deleterious variants of this gene from three pediatric patients: two were novel, and one was a recurrent missense variant previously reported in other pediatric patients.

Exome Sequencing Identified CCER2 as a Novel Candidate Gene for Moyamoya Disease.

The etiology of Moyamoya disease (MMD) is still largely unclear, despite identification of RNF213 as the most significant susceptibility gene in East Asian patients. Following up our previous study confirming genetic heterogeneity in Japanese patients with MMD, we extensively surveyed novel candidate genes for a new perspective on the etiology of this disease. Two characteristic pedigrees without susceptibility variants in RNF213 were selected for whole-exome sequencing; 1 harbored 3 affected members, and the other included discordant monozygotic twins. In the former pedigree, 12 rare mutations in 12 genes were co-segregated with MMD. One of the most deleterious amino acid changes among these was p.T76_G80delinsPS in CCER2, which was also mutated in the latter pedigree (p.E242K), although the unaffected twin sister shared the same mutation reflecting reduced penetrance. These CCER2 mutations were predicted to promote aggregation or oligomerization of their protein product, using in silico functional analysis. Subsequent CCER2 re-sequencing in an additional 135 MMD probands identified 1 recurrent and an additional 2 in-frame insertion-deletion mutations, recurrent p.T76_G80delinsPS, p.H218_H220del, and p.E299del. Although CCER2 molecular function is not well characterized, it is a secretory protein expressed in the brain; therefore, it constitutes a potential biomarker of MMD.

Association of Rare Nonsynonymous Variants in PKD1 and PKD2 with Familial Intracranial Aneurysms in a Japanese Population.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) caused by deleterious mutations in PKD1 (16p13.3) and PKD2 (4q21) often coexists with intracranial aneurysms (IAs). In this study, we investigated whether IAs without obvious renal diseases were also associated with these ADPKD genes. METHODS: We performed next-generation sequencing of the ADPKD genes in 150 Japanese familial IA patients and age- and sex-matched 150 non-IA controls without obvious renal diseases. Rare coding variants for the following association analysis were defined according to allelic frequencies of less than .5% either in our controls or in the 1000 genomes database. Association with IA was evaluated using burden and variance component methods: the weighted-sum statistic (WSS) and the sequence kernel association test (SKAT), respectively. RESULTS: A total of 44 rare candidate variants were confirmed by Sanger sequencing; 26 were identified from 33 patients, whereas 21 were identified from 20 controls. The candidate variants were all missense variants, except for 1 patient's nonsense variant (p.Q924X) in PKD2, and showed consistent association with IA in both burden and variance component tests (odds ratio [OR] = 1.80; WSS, P = .026; SKAT, P = .044). This association was largely derived from the variants found in the extracellular structural domains of PKD1 (OR = 2.06; WSS, P = .030; SKAT, P = .029). CONCLUSION: ADPKD genes are susceptibility genes for IA even in patients without ADPKD.

In vivo semi-automatic segmentation of multicontrast cardiovascular magnetic resonance for prospective cohort studies on plaque tissue composition: initial experience.

Automatic in vivo segmentation of multicontrast (multisequence) carotid magnetic resonance for plaque composition has been proposed as a substitute for manual review to save time and reduce inter-reader variability in large-scale or multicenter studies. Using serial images from a prospective longitudinal study, we sought to compare a semi-automatic approach versus expert human reading in analyzing carotid atherosclerosis progression. Baseline and 6-month follow-up multicontrast carotid images from 59 asymptomatic subjects with 16-79 % carotid stenosis were reviewed by both trained radiologists with 2-4 years of specialized experience in carotid plaque characterization with MRI and a previously reported automatic atherosclerotic plaque segmentation algorithm, referred to as morphology-enhanced probabilistic plaque segmentation (MEPPS). Agreement on measurements from individual time points, as well as on compositional changes, was assessed using the intraclass correlation coefficient (ICC). There was good agreement between manual and MEPPS reviews on individual time points for calcification (CA) (area: ICC; 0.85-0.91; volume: ICC; 0.92-0.95) and lipid-rich necrotic core (LRNC) (area: ICC; 0.78-0.82; volume: ICC; 0.84-0.86). For compositional changes, agreement was good for CA volume change (ICC; 0.78) and moderate for LRNC volume change (ICC; 0.49). Factors associated with LRNC progression as detected by MEPPS review included intraplaque hemorrhage (positive association) and reduction in low-density lipoprotein cholesterol (negative association), which were consistent with previous findings from manual review. Automatic classifier for plaque composition produced results similar to expert manual review in a prospective serial MRI study of carotid atherosclerosis progression. Such automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers.

Perioperative and Long-term Outcomes of Carotid Endarterectomy for Japanese Asymptomatic Cervical Carotid Artery Stenosis: A Single Institution Study.

As the recently developed medical treatments for asymptomatic cervical carotid artery stenosis (ACCAS) have shown excellent stroke prevention, carotid endarterectomy (CEA) should be carried out for more selected patients and with lower complication rates and better long-term outcomes. We have performed CEA for Japanese ACCAS patients with a uniform surgical technique and strict perioperative management. In this study, we retrospectively investigated the perioperative complications and long-term outcomes of our CEA series. A total of 147 CEAs were carried out in 139 Japanese ACCAS patients. All patients were routinely checked for their cardiac function and high risk coronary lesions were preferentially treated before CEA. All CEAs were performed under general anesthesia using a shunt system. The postoperative cerebral blood flow was routinely measured under continued sedation to prevent postoperative hyperperfusion. The 30-day perioperative morbidity rate was 2.04%, including a perioperative stroke rate of 0.68%. There were no perioperative deaths. With regard to the long-term outcomes of the 134 followed-up patients, 9 patients were dead and 5 patients suffered from strokes, including 2 patients with ipsilateral hemispheric ischemia. The annual rates of death, all stroke and ipsilateral ischemic stroke were 1.15%, 0.64%, and 0.25%, respectively. These results showed that the perioperative morbidity and mortality rates of our CEAs were lower than those in the previous large trials. Furthermore, the long-term outcomes of this series were favorable to those reported in the latest medical treatment trials for ACCAS patients. CEA may be useful for preventing ischemic stroke in Japanese ACCAS patients.

Systematic Validation of RNF213 Coding Variants in Japanese Patients With Moyamoya Disease.

BACKGROUND: A founder variant of RNF213, p.R4810K (c.14429G>A, rs112735431), was recently identified as a major genetic risk factor for moyamoya disease (MMD) in Japan. Although the association of p.R4810K was reported to be highly significant and reproducible, the disease susceptibility of other RNF213 variants remains largely unknown. In the present study, we systematically evaluated the coding variants detected in Japanese patients and controls for associations with MMD. METHODS AND RESULTS: To detect variants of RNF213, all coding exons were sequenced in 27 Japanese MMD patients without p.R4810K. We also validated all previously reported variants in our case-control samples and tested for associations in combination with previous Japanese study cohorts, including the 1000 Genomes Project data set, as population-based controls. Forty-six missense variants other than p.R4810K were identified among 370 combined patients and 279 combined controls in Japan. Sixteen of 46 variants were polymorphisms with minor allele frequency >1%, and, after conditioning on the p.R4810K genotype, were not associated with MMD. We conducted a variable threshold test using Combined Annotation-Dependent Depletion on the remaining 30 rare variants (minor allele frequency <1%), and the results showed that the frequency of potentially functional variants was significantly higher in patients than in controls (permutation, minimum P=0.045). CONCLUSIONS: Not only p.4810K but also other functional missense variants of RNF213 conferred susceptibility to MMD. Our analysis also revealed that ≈20% of Japanese MMD patients did not harbor susceptibility variants of RNF213, indicating the presence of other susceptibility genes for MMD.

Omnidirectional retractor-supporting ring as a new device for carotid endarterectomy.

In carotid endarterectomy (CEA), the traditional retractors are often difficult to use because they tend to obstruct surgical manipulations, especially in the deep operative field on the rostral side. The authors have invented a new omnidirectional retractor-supporting ring (OD ring) to solve the problems of traditional retractors. The OD ring has an ellipsoid-shaped frame (major axis: 275 mm, minor axis: 192 mm) with 22 equally spaced outward protrusions. Rubber bands from which blunt mini-hooks are hung are twisted around the protrusions. The OD ring was placed on the operative area, and the skin edges were retracted by mini-hooks placed symmetrically. The hooks were moved gradually from the shallow to the deep operative field as surgical dissection continued to expose the carotid bifurcation and distal internal carotid artery (ICA). The OD ring was used in 158 consecutive CEAs in the authors' institute between July 2010 and October 2013. The OD ring provided a flatter surgical field and was less obstructive than traditional retractors, thereby facilitating surgical manipulation in the deep operative field such as at the distal ICA. Furthermore, because of its simpler shape, angiorrhaphy could be conducted more smoothly, with less tangled thread during closure of the arteriotomy. There were no technical complications related to the OD ring. As a new retractor system for CEA, the OD ring is less obstructive and provides a flatter surgical field than traditional retractors, thereby facilitating surgical manipulations in the deep operative field around the distal ICA.

Gene expression profiling reveals distinct molecular signatures associated with the rupture of intracranial aneurysm.

BACKGROUND AND PURPOSE: The rupture of intracranial aneurysm (IA) causes subarachnoid hemorrhage associated with high morbidity and mortality. We compared gene expression profiles in aneurysmal domes between unruptured IAs and ruptured IAs (RIAs) to elucidate biological mechanisms predisposing to the rupture of IA. METHODS: We determined gene expression levels of 8 RIAs, 5 unruptured IAs, and 10 superficial temporal arteries with the Agilent microarrays. To explore biological heterogeneity of IAs, we classified the samples into subgroups showing similar gene expression patterns, using clustering methods. RESULTS: The clustering analysis identified 4 groups: superficial temporal arteries and unruptured IAs were aggregated into their own clusters, whereas RIAs segregated into 2 distinct subgroups (early and late RIAs). Comparing gene expression levels between early RIAs and unruptured IAs, we identified 430 upregulated and 617 downregulated genes in early RIAs. The upregulated genes were associated with inflammatory and immune responses and phagocytosis including S100/calgranulin genes (S100A8, S100A9, and S100A12). The downregulated genes suggest mechanical weakness of aneurysm walls. The expressions of Krüppel-like family of transcription factors (KLF2, KLF12, and KLF15), which were anti-inflammatory regulators, and CDKN2A, which was located on chromosome 9p21 that was the most consistently replicated locus in genome-wide association studies of IA, were also downregulated. CONCLUSIONS: We demonstrate that gene expression patterns of RIAs were different according to the age of patients. The results suggest that macrophage-mediated inflammation is a key biological pathway for IA rupture. The identified genes can be good candidates for molecular markers of rupture-prone IAs and therapeutic targets.

Hemodynamics and changes after STA-MCA anastomosis in moyamoya disease and atherosclerotic cerebrovascular disease measured by micro-Doppler ultrasonography.

Moyamoya disease (MMD) and atherosclerotic cerebrovascular disease (ACVD) differ in angiographic appearance and probably hemodynamics. Pediatric MMD (PMMD) usually presents with cerebral ischemia, while intracranial hemorrhage is more common in adult MMD (AMMD), suggesting differences in cerebral hemodynamics. We analyzed the cortical flow velocity and direction of recipient arteries using micro-Doppler ultrasonography to evaluate the cortical circulation before and after anastomosis in MMD and ACVD. Twenty-eight patients with adult MMD (AMMD), 7 with pediatric MMD (PMMD), 16 with ACVD, and 12 control patients were studied. A micro-Doppler probe was applied on the cortical recipient artery (A4 or M4) before and after anastomosis. Systolic maximum flow velocity (V max) and blood flow direction were investigated at proximal and distal parts of anastomosed sites in recipient arteries. Pre- and postoperative regional cerebral blood flow was measured by cold xenon-computed tomography (Xe-CT). Before anastomosis, retrograde cortical flow was significantly more common in PMMD patients, and V max in cortical artery was significantly lower in AMMD patients. Bypass surgery changed the direction of blood flow from the anastomosis site to proximal and distal sites of the recipient artery in most patients, but pre-anastomosis flow direction was preserved more frequently in PMMD patients. The rate of V max increase after anastomosis was significantly higher in AMMD than in PMMD (11.6 ± 9.8 vs. 3.9 ± 1.8; P = 0.01). Micro-Doppler ultrasonography identified differences in cortical circulation among AMMD, PMMD, and ACVD. In AMMD, significantly low velocity in the cortical artery was observed before anastomosis, and bypass surgery reversed the flow and significantly increased flow velocity. The data of PMMD showed unique hemodynamics of the cortical artery before anastomosis, characterized by a higher frequency of retrograde flow and preserved velocity. The V max increase rate was significantly higher in patients with postoperative cerebral hyperperfusion on Xe-CT, and further study is warranted to validate the clinical use of intraoperative micro-Doppler monitoring to predict postoperative hyperperfusion.

Analysis of TGFB1 in European and Japanese Moyamoya disease patients.

BACKGROUND: Despite large efforts in researching the genesis of Moyamoya disease (MMD), the etiology of this rare disease remains widely unknown. In a previous publication we described two genetic variants in the first exon of transforming growth factor beta 1 (TGFB1) which were associated and showed a tendency toward significance, respectively. In this study we performed a follow-up analysis of TGFB1 by sequencing the complete exon 1 in European and by genotyping previously described positively associated single nucleotide polymorphisms (SNPs) in Japanese patients with MMD. METHODS: The complete first exon of TGFB1 was genotyped in 40 MMD patients and 68 healthy controls from central Europe. For verification, genotyping of the previously described SNPs rs1800470 and rs1800471 was performed in 45 Japanese MMD patients and 79 healthy controls. Analysis was performed by capillary sequencing with custom made primers. RESULTS: Sequencing of the first exon of TGFB1 in the European cohort did not reveal any new disease-associated nor other genetic variations. The previously described disease association of rs1800471 and tendency toward significance of rs1800470 could not be replicated in the Japanese cohort. CONCLUSIONS: As no new genetic variants were uncovered in this study of the first exon of TGFB1 in European MMD patients and because of the negative association of rs1800470 and rs1800471 in Japanese MMD patients, a role of this exon of TGFB1 in the genesis of MMD is unlikely. Further analyses with even larger cohorts may be necessary to detect causal genetic factors that contribute to the genesis of this disease.

Technical options for the surgical management of extracranial carotid artery aneurysms. Three case reports.

Three cases of extracranial carotid artery (ECA) aneurysm were treated with various surgical options. Two female patients (74 and 37-year-old women) presented with pulsatile masses in their necks, which were confirmed as ECA aneurysms. Another 65-year-old woman presented with a calcified mass in her neck caused by an ECA aneurysm. The first case was treated with aneurysmorrhaphy with primary closure, the second with replacement of the involved site with vascular prosthesis, and the third with a high flow bypass with proximal ligation of the internal carotid artery. All three different surgical techniques were successful. ECA aneurysms are rare and require careful selection of the surgical method according to etiology, shape, and location of the ECA aneurysm. Proficiency in various vascular reconstruction techniques is a desirable prerequisite for the surgeon in-charge.

[Neuromyelitis optica spectrum disorder: a case report].

Neuromyelitis optica (NMO) is a relapsing inflammatory disease of the central nervous system, usually affecting the optic nerves and the spinal cord. It is presumed to be an antibody-mediated disorder and the target antigen is the water channel aquaporin-4 (AQP4) on astrocyte cell membranes. NMO is a disease caused by astrocyte disorder and is distinct from multiple sclerosis (MS), which is a primarily demyelinating disease caused by oligodendrocyte disorder. In NMO, spinal MRI shows a T2-hyperintense, longitudinally extensive (≥ 3 vertebral segments) spinal cord lesion. The case, which has optic neuritis or transverse myelitis with the presence of AQP4 antibody, is called as NMO spectrum disorder. A 68 year-old woman with a history of hypertension and diabetes mellitus was brought to the former hospital by ambulance with acute onset of tetraparesis. She denied visual acuity disturbance. MRI revealed a T2-hyperintense lesion from C5 to T2 level. Laboratory examination showed the presence of AQP4 antibody and the absence of oligoclonal bands. Low-dose steroid treatment was started after establishing a diagnosis of NMO. She incompletely recovered from disability, although the T2-hyperintense lesion on MRI had almost disappeared six months after the onset. It is important to maintain a high index of suspicion for NMO in cases with a longitudinally extensive spinal cord lesion, because untreated NMO leads to severe disability.

[Two cases of iatrogenic vertebral arteriovenous fistulas successfully treated by surgery].

Cervical vertebral arteriovenous fistulas (AVFs) are very rare. The most frequent cause is trauma including iatrogenesis which result from vertebral artery penetration during central venous catheterization. Some endovascular techniques have been reported for this type of lesion. However, several potential problems exist, such as possibility of recurrence of AVFs and VA occlusion with endovascular treatment. In this article, we review two cases with iatrogenic vertebral AVFs which were successfully treated surgically and report the advantages of surgical treatment.

Postcarotid endarterectomy cerebral hyperperfusion can be prevented by minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation.

OBJECTIVE: Cerebral hyperperfusion syndrome is a major complication after carotid endarterectomy (CEA). We investigated whether our strategy of minimizing intraoperative cerebral ischemia and strict postoperative blood pressure control under continuous sedation prevented postoperative hyperperfusion. METHODS: Eighty consecutive patients undergoing CEA were studied. A shunt was used in all patients during CEA. All patients were managed postoperatively under continuous sedation for as long as 48 hours on the basis of the regional cerebral blood flow (rCBF) measured immediately after CEA. Postoperative hyperperfusion was assessed, on the basis of the cerebral blood flow study under sedation (propofol) after CEA, either as a greater than 30% increase in rCBF compared with the contralateral side, or a greater than 100% increase in the corrected rCBF (calculated from percentage reduction of the contralateral rCBF induced by propofol) compared with preoperative values. RESULTS: No patient developed cerebral hyperperfusion syndrome. Postoperative hyperperfusion was found at very low rates (2.5% in the middle cerebral artery territory and 1.3% in the anterior cerebral artery territory by definition 1, and 0% in both territories by definition 2). Ratios of regional oxygen saturation after internal carotid artery clamping to preclamp baseline values were greater than 0.9 in 78 of 80 patients, indicating very mild intraoperative cerebral ischemia. Parameters related to cerebral ischemia during CEA, such as regional oxygen saturation, internal carotid artery cross-clamping duration, and stump pressure (index), did not affect the incidence of postoperative hyperperfusion. CONCLUSION: The present study suggests that minimizing intraoperative cerebral ischemia using a shunt, followed by strict postoperative blood pressure control under continuous sedation, can prevent post-CEA hyperperfusion.

[Genetic dissection of intracranial aneurysm].

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm (IA) is a devastating condition with high mortality and morbidity. Genetic as well as environment factors play important roles in the pathogenesis of SAH and IAs. We review the present knowledge on the genetic factors responsible for SAH or IAs. Linkage analysis and association study are used for genetic dissection. Genome-wide linkage analyses have specified several genetic loci for IAs and 6 loci (1p34-36, 7q11, 11q24-25, 14q22-31, 19q13, and Xp22) have been replicated in different populations. Numerous functional and/or positional candidate genes for IAs have been investigated by case-control association studies. The results of genetic association studies are modest because of small sample sizes. To date, no specific genes have been identified as responsible for IA development or rupture. Recent, large-scale genome-wide association (GWA) studies have revealed consistent and replicable genetic markers of several complex diseases such as coronary artery disease and type 2 diabetes. Although, thus far, no GWA studies have been performed for IAs, such a study may accomplish the breakthrough of genetic dissection of IAs. The identification of susceptible genes might lead to the understanding of the mechanism of IA formation or rupture and to novel therapeutic strategies.