Genetics in Peripheral Artery Disease

Amir-Houshang Shemirani,Zoltán Csiki,András Jávor,Katalin Szilvia Zsóri

doi:10.5772/intechopen.77209

Abstract

Besides traditional risk factor, it has been proved that genetics and gene–environment interaction have a possible independent role in the development and progression of peripheral arterial disease (PAD). Knowledge about such genetic factors will increases our understanding about pathophysiologic mechanisms of PAD and could facilitate the therapeutic approaches. Human genetics has gone through an advanced improvement and it increases our chance to acquire better diagnostic and therapeutic approaches. In this chapter, we try to provide an update on the genetics of PAD, which is mostly about genome-wide association studies, linkage analyses, heritability, candidate gene studies, and epigenetics. Finally, we discuss challenges and future developments of researches in PAD genetics.

Highlights

DNA could go through methylation, histone post-translational modifications, or microRNAs, long noncoding RNA mechanisms [34, 35]. miRNAs are small (≈22 nucleotides) singlestranded RNAs that inhibit translation of mRNA after binding to a target gene
As multiple atherogenic pathways are involved in the pathophysiology of peripheral arterial disease (PAD), a profound monogenic effect is unlikely [46]
Environmental influences such as age, smoking, sport, ethnicity, and diabetes mellitus status besides genetic effects could vary the outcome for this disease

Summary

Introduction

Besides environmental risk factors (e.g., smoking, gender, age), some heritable risk factors are described for atherosclerosis. These are included hyperlipidemia, hypertension and diabetes mellitus. Earlier studies suggested heritability of PAD [1–4]. One study on monozygotic and dizygotic pairs revealed that with the similar environmental risk factors 48% variability of Ankle brachial Index (ABI) could be explained by additive genetic effects [2]. 108 Peripheral Arterial Disease - A Practical Approach (Genetic Epidemiology Network of Arteriopathy) and the Framingham Offspring cohort study found heritability in ABI variations [3, 4]. The degree of genetic variations on the PAD, regardless of the influences of other risk factors, remains to be revealed

Linkage analysis

Genome-wide association study

Candidate gene studies

Epigenetics

Whole genome/exome sequencing

Mendelian randomization

Findings

Discussion