Protein S Gene Mutation: Potential Mechanism of Cerebral Venous Sinus Thrombosis in Patients With Dural Arteriovenous Fistula

BACKGROUND AND OBJECTIVES: Dural arteriovenous fistula (DAVF) is a rare cerebrovascular disease, but current studies have not revealed its etiology. The aim of our study was to explore the relationship between single-nucleotide polymorphisms, DAVF formation, and angioarchitecture. METHODS: This study included 118 DAVF patients who received treatment and underwent genetic sequencing at our hospital. We sequenced the exons of 7 genes and investigated correlations between single-nucleotide polymorphisms, testing results, and clinical characteristics. RESULTS: Among 118 patients (70.3% male, mean age 45.6 years), transverse/sigmoid sinus was the most common shunt location (47.5%). Pial feeders were present in 43.2% of cases, and 39.8% had cerebral venous sinus thrombosis (CVST). Genetic sequencing revealed 22 nonsynonymous mutations, with the PROS1 gene accounting for 9 sites. Pial feeders were associated with lower D-dimer levels ( P = .012) and higher prothrombin time and international normalized ratio values ( P = .012 and .004). CVST cases had lower protein S and adenosine diphosphate platelet aggregation levels ( P = .016 and .042) and higher prothrombin time/international normalized ratio values ( P = .040 and .047). Risk analysis indicated that MTHFR c.665 T/T carriers had reduced risks of pial feeders and high Borden grade DAVFs, whereas PROS1 c.2097 A/G and G/G genotypes were linked to elevated CVST risk. CONCLUSION: This study represents the most comprehensive study of DAVF genetic characteristics to date, featuring the broadest range of genes and the largest patient cohort. Protein S levels are significantly reduced in DAVF patients with CVST, and the PROS1 c.2097 A>G polymorphism is identified as a significant risk factor of sinus thrombosis in these patients.