Abstract TMP17: Polymorphisms In DNA Methylated Genes And Risk Of Intracranial Hemorrhage In Brain Arteriovenous Malformation Patients

Stroke, Volume 54, Issue Suppl_1, Page ATMP17-ATMP17, February 1, 2023. Background:Brain arteriovenous malformations (BAVMs) are a tangle of abnormal vessels that directly shunt blood from the arterial to venous circulation and are a significant cause of intracranial hemorrhage (ICH). DNA methylation, an epigenetic mechanism, can regulate gene expression. Previous studies revealed significant correlations between BAVM development and DNA methylation levels of gene promoter regions inWTAP,METTL3,NOS1AP,PLA2G7,CDKN2A,CDKN2B, andPDGFD. Therefore, we investigated whether genetic variants in these candidate genes are associated with risk of ICH at clinical presentation in BAVM patients.Methods:A total of 383 single nucleotide polymorphisms (SNPs) were investigated using genome-wide data from 338 BAVM Caucasian patients, mapping within 20kb of the genes:WTAP(n=15),METTL3(n=12),NOS1AP(n=190),PLA2G7(n=15),CDKN2A/CDKN2B(n=22), andPDGFD(n=129). We used multivariable logistic regression analysis, adjusting for age, sex, and 3 principal components to adjust for population stratification. The Bonferroni method was used to correct for multiple comparisons (p=0.05/383 SNPs=0.00013). RegulomeDB scores were used to identify putative functional variants.Results:Two SNPs were associated with increased risk of ICH with BAVM at nominal p

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Febbraio 2023