Rare Variants and Polymorphisms of FBN1 Gene May Increase the Risk of Non-Syndromic Aortic Dissection

Aortic dissection (AD) is a cardiovascular disease characterized by high mortality and poor prognosis. Although FBN1 is associated with syndromic AD, its association with non-syndromic AD remains unclear. In this study, DNA samples from 90 Chinese individuals with non-syndromic AD (60 Stanford A, 30 Stanford B types) were analyzed to determine the relationship between diverse genotypes of the FBN1 gene and non-syndromic AD. Eleven pathogenic/likely pathogenic variants (1 novel) were identified in 12.2% of patients with non-syndromic AD. Patients with positive variants suffered from AD at a younger age than those in the negative variant group. Among the six positive missense mutations associated with cysteine residue hosts, four (66.7%) were Stanford A AD, whereas two (33.3%) were Stanford B AD. Three (100%) positive splicing/truncation variant hosts were Stanford A AD. The splicing/truncation variants and missense variants involving cysteine residues in the FBN1 gene increased the risk of Stanford A AD. Ten common SNPs that increased susceptibility to AD were identified. In particular, five SNPs were detected significantly in Stanford A AD, whereas another four SNPs were significantly detected in Stanford B AD. These significant variants can function as biomarkers for the identification of patients at risk for AD. Our findings have the potential to broaden the database of positive mutations and common SNPs of FBN1 in non-syndromic AD among the Chinese population.

Automated summary

This study investigates the association between the FBN1 gene and non-syndromic AD. Pathogenic variants were found in 12.2% of non-syndromic AD patients. Positive variants were associated with younger age of AD onset. Missense mutations involving cysteine residues and splicing/truncation variants in the FBN1 gene increased the risk of Stanford A AD. Additionally, common SNPs were identified that increased susceptibility to AD and could serve as biomarkers for identifying at-risk patients.