Causal association between circulating inflammatory proteins and peripheral artery disease: a bidirectional...

Area of Science:

• Genetics
• Immunology
• Cardiovascular Disease

Background:

• Circulating inflammatory proteins are increasingly linked to Peripheral Artery Disease (PAD).
• The causal relationship between these proteins and PAD requires further investigation.
• Genetic studies offer a powerful approach to elucidate these complex associations.

Purpose of the Study:

• To investigate the bidirectional causal relationship between circulating inflammatory proteins and Peripheral Artery Disease (PAD) using a Mendelian randomization approach.
• To identify specific inflammatory proteins that causally influence PAD risk.
• To determine if PAD causally affects the levels of circulating inflammatory proteins.

Main Methods:

• Bidirectional Mendelian randomization study design.
• Utilized genome-wide association study (GWAS) data for PAD and 91 inflammatory proteins.
• Employed inverse variance weighting (IVW), MR Egger regression, and weighted median approaches for causal inference.

Main Results:

• Elevated Natural Killer cell receptor 2B4 levels were associated with increased PAD risk (OR, 1.219; P=0.03).
• Higher Fractalkine levels were associated with decreased PAD risk (OR, 0.755; P=0.025).
• Peripheral Artery Disease (PAD) showed a significant causal effect on 12 inflammatory proteins, including C-C motif chemokine 19 and T-cell surface glycoprotein CD5.

Conclusions:

• This study provides genetic evidence supporting a causal link between specific circulating inflammatory proteins and Peripheral Artery Disease (PAD).
• Findings highlight Natural Killer cell receptor 2B4 and Fractalkine as potential players in PAD etiology.
• The bidirectional relationship suggests complex interactions between inflammation and PAD, informing future research directions.