关键词:

CDKN2A/B 基因, 颅内动脉瘤, SNP 位点, 动脉瘤壁组织

Abstract:

Objective Intracranial aneurysm is a complex disease induced by the interplay of genes and environmental factors，commonly leading to fatality and disability. The purpose of this study was to explore the corre⁃ lation between CDKN2A/B gene polymorphism and intracranial aneurysm formation. Methods Eighty⁃two patients with clipped aneurysm and one hundred and fourteen patients with non ⁃intracranial aneurysm were enrolled. SNP genotyping was used to analyze the single nucleotide polymorphisms（SNP）related to CDKN2A/B. RT ⁃ PCR and Western Blot were used to detect gene translation and expression in aneurysm walls and immunofluorescence was used to compare the volumes of protein expression of the genes. Results The p15INK4b/p16INK4a protein that CDKN2A/B gene expressed was detected in the aneurysm walls，and the frequency of allele T at rs10757272 was higher than that in the control group（P = 0.029，OR，1.658；95%CI，1.051 ~ 2.614）. The p16INK4a and p15INK4b mRNAs at rs10757272 locus were transcribed at a low level in the T/T genotype aneurysmal wall tissues（P < 0.001 and 0.014，respectively），and the p15INK4b was expressed in T/T genotype at a low level（P = 0.027）. However， there was no significant difference in the expression level of p16INK4a（P = 0.089）in spite of presenting a similar trend of low expression. The immunofluorescent staining of aneurysm wall tissues showed the identical results. Conclusion The mutation of SNP at rs10757272 participates in the formation of intracranial aneurysms by interven⁃ ing the expression of CDKN2A/B and thereby affecting the plasticity of the aneurysm wall tissue cells.

Key words:

CDKN2A/B, intracranial aneurysms, SNP, aneurysm wall tissue