| 1.Background and Purpose: Subarachnoid hemorrhage(SAH), caused by rupture of intracranial aneurysm(s)(IA), is a critical complication of neurosurgery. However, there have been few reports examining the genes related to risk factors that may contribute to IAs. The current study aims to explore the allele frequencies and genotype frequency distributions of the SNPs in genes of the intracranial aneurysm risk factor among intracranial aneurysms patients in the Chinese Han population, to explore the relationship between Chinese IA patients and 28 gene loci, which have proven to be associated with risk factors for IA.2.Methods and methods2.1 Object of study: We recruited 119 patients with aneurysms and 257 control subjects. In the IA group, DNA extraction and SNP genotyping passed QC measures for 116 subjects, while in the control group, informative results were obtained from 251 subjects. The aneurysmal patients were collected from neurosurgery ward in Tianjin Medical University General Hospital from 2013 to 2014. They were confirmed by clinical symptoms and then subject to whole brain digital subtraction angiography or CT angiography for the diagnosis of intracranial aneurysms. The control group was 257 healthy Han people from our hosptital’s medical department. We selected candidate SNPs associated with epidemiologic risk factors for IA as those having a P < 5×10–8 from published genome-wide association studies(GWAS). Our primary analyses examined 28 SNPs associated with well-established IA risk factors, including hypertension, hypercholesterolemia, obesity, T2 DM, gout, polycystic kidney disease, and inflammation. 2.2 Research Methods: The clinical data of hosptialized patients with intracranial aneurysms and control group were all recorded into Excel. Whole blood genomic DNA was extracted using Bioteke whole genomic DNA extraction kit. Then it was measured concentration in the Nanodrop ND-2000 spectrophotometer. PCR primers of the corresponding SNP loci were designed according to the nucleotide sequences in NCBI database, then they were used to amplify the sequences which will later usedfor sequencing in Bio Miao companies. 2.3 Statistical analysis: Chi-square test of the SPSS statistical software were used to analysis the allele frequencies. The allele frequencies of the 28 SNP loci in 22 genes between cases and controls were compared with the 2c test. Mean plus or deviation standard deviation were show for Measurement data. They were compared using univariable analyses. P<0.05 was considered statistically significant. The progressive model of “Logist regression model” were used to identify the IA risk factors of primary effect and assess whether there is a cumulative effect between risk factors for intracranial aneurysms.3.ResultsOur study collects 119 study group intracranial aneurysms patients with male 49 cases(41.2%), female 70 cases(58.8%), mean age(53.34±11.42) years. Using univariable analyses, there were no statistically significant differences between groups with respect to age, hypercholesterolemia, smoking and alcohol consumption. There were no statistically significant differences between groups with respect to female, hypertension, diabetes, heart disease. Logistic regression analysis identified hypertension as a factor that increased IA risk(P = 1.0×10-4; OR, 2.500; 95% CI, 1.573-3.972). A total of 138 aneurysms were detected in 119 patients. 103 patients had one aneurysm. Overall, 67 aneurysms(48.6%) were located in the internal carotid artery; 34 aneurysms(24.6%) were located in the anterior cerebral and anterior communicating arteries; Intracranial saccular aneurysms were found in 122(88.4%) of the 138 aneurysms. There are 82 patients of ruptured aneurysm and 37 patients of unruptured aneurysm. Using univariable analyses, there were statistically significant differences between groups with respect to age and hypertension. Univariate analysis determined that there were not associated with an increased risk of aneurysm rupture. 2) To compare the allele frequencies of the 28 SNP loci in 22 genes between cases and controls, We found that IA was associated with two SNPs: in the TSLC2A9 gene: rs7660895(P = 0.007; OR, 1.541; 95% CI, 1.126-2.110); and in the TOX gene: rs11777927(P = 0.013; OR, 1.511; 95% CI, 1.088-2.098). Subsequent removal of the influence of family relationship identified between 12 of 119 patients enhanced thesignificant association of these SNPs with IA(P = 0.001; OR, 1.691; 95% CI, 1.226-2.332; and P = 0.006; OR, 1.587; 95% CI, 1.137-2.213 for rs7660895 and rs11777927, respectively). Furthermore, to explore the allele frequencies of rs7660895 and rs11777927 in ruptured and unruptured, we found the minor allele of rs7660895(A) was also associated with IA rupture(P = 0.007; OR, 2.196; 95% CI, 1.230-3.921). But rs11777927 was not(P=0.594,OR, 1.173; 95%CI,0.652- 2.113).Conclusion: Hypertension is an independent risk factor for IA. Our study also indicated that the TSLC2A9(rs7660895) and TOX(rs11777927) gene polymorphisms may be associated with formation of IAs, and importantly, that rs7660895 may be associated with IA rupture. |
PDF Full Text Request