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

Abstract

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. 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. 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. 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.