Systematic review and meta-analysis of the genetics of peripheral arterial disease

Peripheral artery disease (PAD) impacts more than 200 million people worldwide. The understanding of the genetics of the disease and its clinical implications continue to evolve. This systematic review provides a comprehensive summary of all DNA variants that have been studied in association with the diagnosis and progression of PAD, with a meta-analysis of the ones replicated in the literature. A systematic review of all studies examining DNA variants associated with the diagnosis and progression of PAD was performed. Candidate gene as well as genome wide association studies (GWAS) were included. A total of 231 DNA variants in 112 papers were studied for the association with the diagnosis of PAD. There were significant variations in the definition of PAD and the selection of controls in the various studies. GWAS have established 19 variants associated with the diagnosis of PAD that were replicated in several large patient cohorts. A meta-analysis of 13 variants derived from earlier smaller candidate gene studies of the diagnosis of PAD was performed. Only variants in ICAM-1 (rs5498), IL-6 (rs1800795), and hepatic lipase (rs2070895) showed significant association with the diagnosis of PAD. However, those variants were not noted in the published GWAS studies. The literature on progression of PAD was limited and a meta-analysis was not feasible because of the heterogeneity in the criteria used to characterize it. Genetic research in the diagnosis of PAD has significant heterogeneity but recent GWAS have demonstrated variants consistently associated with the disease. More research focusing on the progression of PAD is needed to identify patients at risk of adverse events and develop strategies that would improve their outcomes.