| Background: An intracranial aneurysm is a complex disease characterized by pathologic dilatations of the cerebral arteries.Aneurysmal subarachnoid hemorrhage caused by a ruptured intracranial aneurysm has a high mortality and disability rate,which seriously affects human life and health.Rho Guanine Nucleotide Exchange Factor 7(ARHGEF7),it is highly expressed in the brain and blood vessels and can affect the proliferation,migration,adhesion and angiogenesis of vascular endothelial cells.ARHGEF7 also regulates the stability,permeability and integrity of the vascular wall and plays an important regulatory role in the development and maturation of blood vessels.The mutation or deletion of the ARHGEF7 gene can affect the normal development of cerebral blood vessels.In this study,patients with IA were selected as research objects to investigate the relationship between ARHGEF7 gene polymorphism and the incidence,rupture and prognosis of intracranial aneurysms.Methods: These clinical data and blood samples were collected from 150 patients with intracranial aneurysms and 155 controls.DNA of the cases and controls were extracted from peripheral blood.Sequenom Mass ARRAY technology was used to detect 10 genotypes of ARHGEF7 genetic variants in all populations.Binary logistic regression analysis was used to compare the differences in genotypes and allele frequencies of ARHGEF7 genetic variants between the intracranial aneurysm group and the controls group and between the ruptured group and the unruptured group in the intracranial aneurysm group.The correlation between gene polymorphism and prognosis of IA was investigated by Cox regression analysis.Results: There were no significant genetic associations between the tested variants and intracranial aneurysm risk.After adjustment for age,sex,and traditional cardiovascular risk factors,the rs4145274 GA genotype was associated with a decreased rupture risk of intracranial aneurysms as compared with the rs4145274 GG genotype,and the odds ratio was 0.18(95% confidence interval [CI]: 0.06～0.49,P=0.001).The rs1555751 CT genotype was also associated with a decreased rupture risk of intracranial aneurysms as compared with the rs1555751 CC genotype,and the odds ratio was 0.12(95% CI:0.03-0.48,P=0.003).In the sex-specific analysis,the women carrying rs4145274 GA and rs1555751 CT genotypes were more associated with a reduced rupture risk of intracranial aneurysm,and the odds ratio was 0.28(95% CI: 0.14-0.87,P=0.04)and 0.22(95% CI: 0.08-0.62,P=0.004),respectively.The combined effect between rs4145274 and rs1555751 suggested that the patients with an increased genetic risk score had a lower rupture risk of intracranial aneurysms(P<0.05).Patients with IA rupture were followed up for 6 months,and rs4145274 GA genotype was more frequently carried in the favorable prognosis group compared with the poor prognosis group(P < 0.05).At a mean follow-up of 1.5 years,neither rs4145274 nor rs1555751 were associated with the risk of events during IA follow-up.Conclusions: Our study found that ARHGEF7 genetic variants rs4145274,and rs1555751 and their combined effect were associated with a reduced rupture risk of intracranial aneurysm.ARHGEF7 genetic variants may be potential molecular markers for the development of IA.Figures 3 Tables 15 Reference 57... |
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