Genetic association between inflammatory factors and abdominal aortic aneurysm: Insights from a genome-wide association study

Abstract

Background: Abdominal aortic aneurysm (AAA) is a fatal vascular disorder. The current primary treatment for AAA remains restricted to surgical intervention during advanced stages of the disease, with no efficacious pharmaceutical options available for early-stage AAA patients. Inflammation is known to play a substantial role in the development of AAA, with various inflammatory factors implicated in its pathogenesis. However, conflicting findings have been reported in studies investigating the roles of these inflammatory factors in AAA, making it challenging to establish definitive causal relationships between inflammatory factors and AAA.

Methods: The research conducted a bidirectional Mendelian randomization (MR) study using genetic variants. Inflammatory factors were obtained from a genome-wide association study (GWAS), while AAA were sourced from the FinnGen consortium. The primary method employed was inverse-variance weighted (IVW), with MR-Egger, weighted median, and MR-PRESSO approaches used as supplementary analyses.

Results: According to the IVW method, hepatocyte growth factor (HGF), matrix metalloproteinase-7 (MMP-7), MMP-12, and NF-kappa-B essential modulator (NEMO/ IKKγ) were associated with a potential increased risk of AAA, while platelet-derived growth factor BB (PDGFbb), interleukin-4 (IL-4), IL-12p70, IL-10, IL-6Rα, and myeloperoxidase (MPO) were associated with a potential decreased risk of AAA. In the reverse MR analysis, no causal relationship was observed between AAA and any of the inflammatory factors.

Conclusions: This study provides evidence supporting a causal relationship between inflammatory factors and AAA. It suggests that targeting and modulating these specific inflammatory factors may serve as a potential approach for the prevention and noninvasive treatment of AAA.

Keywords: Abdominal aortic aneurysm; Inflammatory factors; Mendelian randomization; Myeloperoxidase; NF-kappa-B essential modulator.