AUTHOR=Wang Zhepei , Zhou Shengjun , Zhao Jikuang , Nie Sheng , Sun Jie , Gao Xiang , Lenahan Cameron , Lin Zhiqin , Huang Yi , Chen Gao 

TITLE=Tobacco Smoking Increases Methylation of Polypyrimidine Tract Binding Protein 1 Promoter in Intracranial Aneurysms

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=13

YEAR=2021

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2021.688179

DOI=10.3389/fnagi.2021.688179

ISSN=1663-4365

ABSTRACT=<p>DNA methylation at the gene promoter region is reportedly involved in the development of intracranial aneurysm (IA). This study aims to investigate the methylation levels of polypyrimidine tract-binding protein 1 (<italic>PTBP1</italic>) in IA, as well as its potential to predict IA. Forty-eight patients with IA and 48 age- and sex-matched healthy controls were recruited into this study. Methylation levels of CpG sites were determined via bisulfite pyrosequencing. The <italic>PTBP1</italic> levels in the blood were determined using a real-time quantitative reverse transcription-polymerase chain reaction test. Significant differences were found between IAs and controls in CpG1 (<italic>p</italic> = 0.001), CpG2 (<italic>p</italic> &lt; 0.001), CpG3 (<italic>p</italic> = 0.037), CpG4 (<italic>p</italic> = 0.003), CpG5 (<italic>p</italic> = 0.006), CpG6 (<italic>p</italic> = 0.02), and mean methylation (<italic>p</italic> &lt; 0.001). The mRNA level of <italic>PTBP1</italic> in the blood was much lower in IAs compared with controls (<italic>p</italic> = 0.002), and the <italic>PTBP1</italic> expression was significantly associated with DNA methylation promoter levels in individuals (<italic>r</italic> = −0.73, <italic>p</italic> &lt; 0.0001). In addition, stratification analysis comparing smokers and non-smokers revealed that tobacco smokers had significantly higher levels of DNA methylation in <italic>PTBP1</italic> than non-smokers (<italic>p</italic> = 0.002). However, no statistical difference in <italic>PTBP1</italic> methylation was found between ruptured and unruptured IA groups (<italic>p</italic> &gt; 0.05). The ROC analyses of curves revealed that <italic>PTBP1</italic> methylation may be a predictor of IA regardless of sex (both sexes, area under curve (AUC) = 0.78, <italic>p</italic> &lt; 0.0001; male, AUC = 0.76, <italic>p</italic> = 0.002; female, AUC = 0.79, <italic>p</italic> &lt; 0.0001). These findings suggest that long-term tobacco smoke exposure led to DNA methylation in the promoter region of the <italic>PTBP1</italic> gene, which further decreased <italic>PTBP1</italic> gene expression and participated in the pathogenesis of IA. The methylation of <italic>PTBP1</italic> may be a potential predictive marker for the occurrence of IA.</p>