The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine

Abstract

Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis.

Observation of the immediate effect of ultrasound-guided acupuncture at Zusanli (ST36) point on Blood flow volume in lower limb arteries: a randomized controlled trial study protocol

“…LEAD (Lower extremity arterial disease, LEAD), also known as lower extremity peripheral artery disease (lower limb peripheral artery disease, PAD), or lower extremity PAD, belongs to a large PAD family. This disease is a chronic obstruction characterized by reduced blood ow to the downward limb artery, leading to ischemia, which may accompany with thromboembolism [20] . The survey indicates that approximately 200 million individuals globally suffer from lower limb arterial vascular lesions (LEAD) [21] .…”

Narrative Review of Biological Markers in Chronic Limb-Threatening Ischemia

“…There are currently a number of genes that are involved in atherosclerosis: genes that are involved in lipid metabolism (APOB on chromosome 2p24.1), genes involved in inflammatory mechanisms in the vascular wall (IL6 gene located on 7p15.3), genes involved in blood pressure regulation (ACE genes), genes involved in the function of Vascular Smooth Muscle Cells, genes involved in the maintenance of vascular homeostasis, or genes that contribute to the process of atherothrombosis. The discovery of the genes involved in the pathophysiological mechanisms of BAP is a step toward finding an early diagnosis as well as a complete and effective treatment of this pathology [84].…”

Association between DNA methylation and smoking in patients with chronic limb - threatening ischemia

“…Aunque en los últimos años han aparecido estudios de epigenética y su relación con la EAP, no hay evidencia de la relación entre la metilación de estos 2 CpG y el riesgo de presentar EAP (24)(25)(26).…”