# Genetic insights into 5-LOX-activating protein: a narrative review of disease associations

## TL;DR

This paper reviews genetic variations in the FLAP protein and their links to diseases like heart disease and stroke.

## Contribution

The paper synthesizes findings on ALOX5AP SNPs and their inconsistent associations with coronary artery disease, myocardial infarction, and ischemic stroke.

## Key findings

- Over 20,000 SNPs in the ALOX5AP gene have been identified, with 66 studied for disease associations.
- Associations between FLAP SNPs and coronary artery disease, myocardial infarction, and ischemic stroke are inconsistent across studies.
- Meta-analyses of FLAP SNPs are limited by differences in study design and populations.

## Abstract

The 5-lipoxygenase-activating protein (FLAP) is an integral membrane protein that is essential for 5-lipoxygenase-mediated leukotriene formation, thereby playing a key role in inflammation and serving as a potential therapeutic target. For over 30 years, researchers have been elucidating the crystal structure, identifying the inhibitor binding site, and developing several potent inhibitors, which have been investigated in preclinical and clinical studies to treat asthma, chronic kidney and cardiovascular diseases. However, despite being almost overlooked, more than 20,000 single nucleotide polymorphisms (SNPs) were detected in the ALOX5AP gene, coding for FLAP. To date, 66 SNPs have been studied in relation to a disease by different researchers, including different population groups. This review aims to synthesize current evidence on genetic variants of FLAP and delineate single SNPs that have been primarily implicated in coronary artery disease, myocardial infarction, and ischemic stroke. Associations between SNPs of ALOX5AP and these diseases have been reported, but findings remain inconsistent due to differences in study design, population diversity and methodological approaches. Although meta-analyses helped to integrate the results of different studies, they remain limited due to underlying differences and cannot provide a definitive conclusion.