{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:07:51Z","timestamp":1777511271009,"version":"3.51.4"},"reference-count":147,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms231810481","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T22:53:46Z","timestamp":1663023226000},"page":"10481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-4244","authenticated-orcid":false,"given":"L\u0103cr\u0103mioara Ionela","family":"Butnariu","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eusebiu Vlad","family":"Gorduza","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Florea","sequence":"additional","affiliation":[{"name":"Department of Nefrology\u2013Internal Medicine, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3018-8011","authenticated-orcid":false,"given":"Elena","family":"\u021aarc\u0103","sequence":"additional","affiliation":[{"name":"Department of Surgery II\u2014Pediatric Surgery, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4140-0492","authenticated-orcid":false,"given":"\u0218tefana Maria","family":"Mois\u0103","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Mihaela","family":"Tradafir","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7859-840X","authenticated-orcid":false,"given":"Elena","family":"Cojocaru","sequence":"additional","affiliation":[{"name":"Department of Morphofunctional Sciences I, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5676-0864","authenticated-orcid":false,"given":"Alina-Costina","family":"Luca","sequence":"additional","affiliation":[{"name":"Department of Mother and Child, Medicine-Pediatrics, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"St\u0103tescu","sequence":"additional","affiliation":[{"name":"Medical III Department-Dermatology, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Ia\u015fi, Romania"},{"name":"Screening Center for Oncological Diseases, Regional Institute of Oncology, 700115 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-1909","authenticated-orcid":false,"given":"Minerva Codru\u021ba","family":"B\u0103descu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 16 University Street, 700115 Ia\u0219i, Romania"},{"name":"III Internal Medicine Clinic, \u201cSt. Spiridon\u201d County Emergency Clinical Hospital, 1 Independence Boulevard, 700111 Ia\u0219i, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/eurheartj\/ehx095","article-title":"2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. 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