Intracranial Aneurysm Group Research Articles

Association of TNF-α-3959T/C Gene Polymorphisms in the Chinese Population with Intracranial Aneurysms.

Recent studies have demonstrated that cytokines play an important role in the pathogenesis of intracranial aneurysm (IA). Tumor necrosis factor-α (TNF-α) is an important proinflammatory cytokine, which was shown to influence the development of IA, but there is no research data from China. Hence, the purpose of this study was to explore the relationship between TNF-α polymorphisms and IA in China. The association of genetic variants of TNF-α gene expression was investigated in a Chinese population with IA. The TNF-α-3959T>C(rs1799964), 4127C>A(rs1800630), 4133C>T(rs1799724), 4184C>T(rs4248158), and 4752G>A(rs361525) gene polymorphisms in 192 IA cases and 112 controls were analyzed using polymerase chain reaction (PCR). Differences in genotype and allele frequencies between patients and controls were tested. There were no significant differences in 4127C>A (p=0.072), 4133C>T (p=0.373), 4184C>T (p=0.749), and 4752G>A (p=0.184) genotype frequencies between the IA group and the control group. But this case-control association study revealed that TNF-α-3959T>C (p<0.001) was significantly associated with increased risk of IA. These results suggested that a novel TNF-α locus was found to be closely correlated with the occurrence of IA in Chinese.

Abstract WP92: Neutrophil-lymphocyte Ratio in Cerebral Aneurysm

Introduction: Blood neutrophil/lymphocyte ratio (NLR) is a simple marker of subclinical inflammation that can be easily obtained. The NLR has recently emerged as a prognostic marker in patients with cancer and coronary artery disease. However, little is known about the role of NLR in patients with intracranial aneurysm (IA). Hypothesis: The purpose of this study was to determine the clinical significance of NLR in patients with IA. Methods: The study group consisted of patients with IA who had been admitted to the neurology department from January 2008 to December 2014. A total of 362 patients including 176 patients with unruptured IA, 186 patient with ruptured IA were enrolled in this study. The control group consisted of 178 age, sex-matched healthy adults who had not harbor IA by CTA, MRA, DSA. The baseline NLR was calculated as the ratio of neutrophil count to lymphocyte count. WBC count&gt;12.000 cells per μL or &lt;4.000 cells per μL and high body temperature&gt;38 ° are excluded from the study. Results: The Mean NLR was significantly higher among persons with cerebral aneurysm compared with controls (P &lt; 0.001). The level of NLR in ruptured IA group were found higher compared to unruptured IA and control group (7.0 ± 6.6 vs 2.5 ± 1.5 vs 1.6 ± 0.5, P &lt; 0.001). Other comorbid conditions were balanced between these three groups. Conclusions: Higher NLR is associated with cerebral aneurysm. Unlike many other inflammatory markers and bioassays, NLR are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm.

Efficacy and Safety of Intravenous Thrombolysis for the Treatment of Acute Ischemic Stroke Patients with Saccular Intracranial Aneurysms of ≤3 mm

To explore the effectiveness and safety of intravenous thrombolysis (IVT) using recombinant tissue plasminogen activator in treating acute ischemic stroke patients with concomitant intracranial aneurysms (IA) of ≤3mm. Clinical data of patients who were treated in Tianjin Huanhu Hospital from June 2012 to September 2013 were retrospectively analyzed. Patients were divided into the following groups: (a) IVT group, in which there were 30 acute ischemic stroke patients with IA of ≤3mm and 30 patients without aneurysms; and (b) IA group, in which there were 30 patients who did not receive IVT and 30 patients who received IVT. The incidence of intracranial hemorrhage, case-fatality, and good outcome rate was compared within these two groups. Inside the IVT group, the incidence of systematic intracranial hemorrhage and case-fatality showed no significant differences between patients with concomitant IA and those without IA. The 3-month good outcome rate was also not significantly different (24 [80.0%] vs. 27 [90%]; P=0.278). In IA group, patients who had received IVT showed significantly superior good outcome rate than those who had not received IVT (24 [80.0%] vs. 16 [53.3%]; P=0.028).The incidence of intracranial hemorrhage and case-fatality rate were not significantly different between these two subgroups as well. IVT is effective and safe method for the treatment of acute ischemic stroke patients with saccular IA of ≤3mm.

Three‐dimensional hemodynamics in intracranial aneurysms: influence of size and morphology

PurposeTo use four‐dimensional (4D)‐flow MRI for the comprehensive in vivo analysis of hemodynamics and its relationship to size and morphology of different intracranial aneurysms (IA). We hypothesize that different IA groups, defined by size and morphology, exhibit different velocity fields, wall shear stress, and vorticity.Materials and MethodsThe 4D‐flow MRI (spatial resolution = 0.99–1.8 × 0.78–1.46 × 1.2–1.4 mm3, temporal resolution = 44–48 ms) was performed in 19 IAs (18 patients, age = 55.4 ± 13.8 years) with saccular (n = 16) and fusiform (n = 3) morphology and different sizes ranging from small (n = 8; largest dimension = 6.2 ± 0.4 mm) to large and giant (n = 11; 25 ± 7 mm). Analysis included quantification of volumetric spatial–temporal velocity distribution, vorticity, and wall shear stress (WSS) along the aneurysm's 3D surface.ResultsThe 4D‐flow MRI revealed distinct hemodynamic patterns for large/giant saccular aneurysms (Group 1), small saccular aneurysms (Group 2), and large/giant fusiform aneurysms (Group 3). Saccular IA (Groups 1, 2) demonstrated significantly higher peak velocities (P &lt; 0.002) and WSS (P &lt; 0.001) compared with fusiform aneurysms. Although intra‐aneurysmal 3D velocity distributions were similar for Group 1 and 2, vorticity and WSS was significantly (P &lt; 0.001) different (increased in Group 1 by 54%) indicating a relationship between IA size and hemodynamics. Group 3 showed reduced velocities (P &lt; 0.001) and WSS (P &lt; 0.001).ConclusionThe 4D‐flow MRI demonstrated the influence of lesion size and morphology on aneurysm hemodynamics suggesting the potential of 4D‐flow MRI to assist in the classification of individual aneurysms. J. Magn. Reson. Imaging 2014;39:120–131. © 2013 Wiley Periodicals, Inc.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and risk of intracranial aneurysm in a Chinese population

The relationship between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphisms and intracranial aneurysm (IA) has been studied in Caucasian and Japanese populations. The present study aimed to investigate this association in a Chinese population. Patients with confirmed IA and age- and sex-matched control subjects without evidence of IA were enrolled. ACE I/D gene polymorphisms were analysed using polymerase chain reaction-restriction fragment length polymorphism. A total of 220 patients with IA and 220 matched controls were enrolled. In the IA group, 64, 106 and 50 patients were of the II, ID and DD genotypes, respectively, compared with 44, 99 and 77 subjects in the control group. The ACE DD genotype and D allele frequencies were significantly lower in the IA group compared with the control group. There were no statistically significant differences in the site, shape, size and Fisher Grade of aneurysms between genotypes in patients with IA. The ACE DD genotype may be a protective factor for IA in a Chinese population.

The Interleukin-6-572G/C Gene Polymorphism and the Risk of Intracranial Aneurysms in a Chinese Population

Interleukin-6 (IL-6) is an important proinflammatory cytokine that plays an important role in the pathogenesis of intracranial aneurysms (IAs). The aim of this study was to investigate the association between the IL-6-572G/C polymorphism and the risk of IAs in a Chinese population. The IL-6-572G/C gene polymorphisms in 220 IA cases and 220 controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. The IL-6-572GG (odds ratio [OR]=3.35, 95% confidence intervals [CIs]=1.65, 6.82; p=0.001) and G allele frequencies (OR=1.48, 95% CIs=1.09, 2.00; p=0.01) in the IA group were higher than those in the control group. The C allele frequencies (OR=0.68, 95% CIs=0.50, 0.92; p=0.01) were significantly lower in patients than in controls. When stratified by the site, shape, size, and the Fisher Grade of IAs, no statistically significant result was observed. This study suggested that the IL-6-572GG genotype was associated with a higher risk of IA in a Chinese population.

Association of interleukin-6-572G/C gene polymorphisms in the Cantonese population with intracranial aneurysms

Recent studies have demonstrated that cytokines play an important role in the pathogenesis of intracranial aneurysms (IAs). Interleukin-6 (IL-6) is an important proinflammatory cytokine. In our study, we investigated the association of genetic variants within the gene encoding interleukin-6-572G/C (IL-6-572G/C) with IAs in the Cantonese population. The IL-6-572G/C gene polymorphisms in 182 IA cases and 182 controls were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences in genotype and allele frequencies between patients and controls were tested. There is significant difference of IL-6-572G/C genotype frequencies in IA group compared with control group (P = 0.01), and significant difference of IL-6-572G/C allele frequency in IA group (11.54%) compared with control group (4.95%) (P = 0.001). Polymorphisms within IL-6-572G/C gene are associated with IAs in the Cantonese population suggesting that the IL-6-572G/C gene is an important candidate gene for IAs.

Gene Expression Profiles in Human Ruptured and Unruptured Intracranial Aneurysms

Mechanisms underlying development and rupture of intracranial aneurysms (IA) are poorly recognized. The majority of studies on human tissue have focused on predefined pathways. We sought to analyze global gene expression patterns of ruptured IA, unruptured IA, and control vessels. Transcription profiles were studied in human ruptured (n=8) and unruptured (n=6) IA, as well as in control intracranial arteries (n=5), using oligonucleotide microarrays. Real-time reverse-transcription polymerase chain reaction was used for confirmation. Functional analysis for determination of over-represented ontological groups among gene expression profiles was also performed. The expression of 159 genes differed among the studied groups. Compared to the controls, 131 genes showed common directions of change in both IA groups. The most impacted biological processes for IA are: (1) the muscle system; (2) cell adhesion (downregulation); and (3) the immune system and inflammatory response (upregulation). Ruptured and unruptured IA differed in genes involved in immune/inflammatory processes; expression was reduced in ruptured IA. Decreased expression of genes related to muscle system and cell adhesion is important for the development of IA. The role of immune/inflammatory processes is unclear. Inflammation may participate in the healing process within IA while playing a protective role against IA rupture.

Endoglin is not a major susceptibility gene for intracranial aneurysm among Japanese.

A 6-base insertion (6bINS) polymorphism in intron 7 of the endoglin gene (ENG), which codes for a component of the transforming growth factor-beta receptor complex, was reported to be associated with intracranial aneurysm (IA) in a Japanese population. A recent report using a white population could not replicate the association. We tested for this association with high statistical power in our independent Japanese subjects and evaluated the linkage between markers on chromosome 9, which contains ENG, and IA. The sample for the linkage study comprised 179 individuals with IA in 85 nuclear families, with 104 possible affected sibpairs. For the association study of the 6bINS polymorphism and 4 single nucleotide polymorphisms (SNPs) in ENG, 172 Japanese patients with IA and 192 control subjects were examined. There was no evidence of linkage in the vicinity of ENG by analysis of affected sibpairs. The allele frequency of the 6bINS polymorphism was 104 of 344 (30.2%) in the total IA group and 122 of 382 (31.9%) in the control group. The statistical difference in allele frequency between the 2 groups was not significant (chi2=0.245, df=1, P=0.620). The power of the present association study was 98.3% at a significance level of 0.05 on the basis of the allele frequencies in the previous study. In addition, no associations between the 4 SNPs in ENG and IA were detected. We provide evidence that there is no association between the 6bINS polymorphism or 4 SNPs in ENG and IA and that there is no linkage between the ENG locus and IA, indicating that ENG is not a major susceptibility gene for IA in Japanese.

Genetic Analysis of MMP3, MMP9, and PAI-1 in Finnish Patients with Abdominal Aortic or Intracranial Aneurysms

MMP3, MMP9, and PAI-1 are present at increased levels in abdominal aortic aneurysms (AAAs). The promoters of these genes contain polymorphisms, with alleles that exhibit different transcriptional activities in vitro. Association studies were performed using these polymorphisms and DNA isolated from 47 AAA patients, 57 intracranial aneurysm (IA) patients, and 174 controls, all from Finland. PAI-1 and MMP9 genotypes did not associate with aneurysms. The frequency of the 5A MMP3 allele was somewhat higher in the AAA than that in the control group (P = 0.0609 after Bonferroni correction), whereas the MMP3 allele frequencies in the IA group did not differ from those of the controls (P = 0.9667). These findings suggest that the transcriptionally more active 5A MMP3 allele might be a genetic risk factor for AAA among Finns. They are in agreement with previous studies demonstrating higher level of MMP3 expression in AAA than in control tissues.

A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada).

The genealogies of 533 individuals with an intracranial aneurysm (IA) born in the Saguenay-Lac-Saint-Jean region, a geographically isolated area located in northeastern Quebec, were reconstructed using a population-based register. A control group consisting of three individuals of the same sex and born on the same day and in the same municipality than the IA patients was created; the genealogies of the 1599 controls were also reconstructed. The coefficients of inbreeding and kinship were calculated. Familial aggregation, i.e. the presence of IA in two or more first- to third-degree relatives, was also sought. The mean inbreeding coefficient was lower in the IA group than in the control group (7.92 x 10(-4) versus 10.04 x 10(-4)). The mean kinship coefficient was higher in the IA group than in the control group (2.17 x 10(-4) versus 1.55 x 10(-4)). Forty-eight IA patients (9.0%) were first-degree relatives compared to only 1.9% of the control individuals. The proportion of individuals showing familial aggregation was higher in the IA group than in the control group (29.8% and 18.6% respectively). These results strongly suggest that some IA are genetically determined in this population.