{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T14:46:14Z","timestamp":1771512374021,"version":"3.50.1"},"reference-count":168,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hypertriglyceridemia is an exceptionally complex metabolic disorder characterized by elevated plasma triglycerides associated with an increased risk of acute pancreatitis and cardiovascular diseases such as coronary artery disease. Its phenotype expression is widely heterogeneous and heavily influenced by conditions as obesity, alcohol consumption, or metabolic syndromes. Looking into the genetic underpinnings of hypertriglyceridemia, this review focuses on the genetic variants in LPL, APOA5, APOC2, GPIHBP1 and LMF1 triglyceride-regulating genes reportedly associated with abnormal genetic transcription and the translation of proteins participating in triglyceride-rich lipoprotein metabolism. Hypertriglyceridemia resulting from such genetic abnormalities can be categorized as monogenic or polygenic. Monogenic hypertriglyceridemia, also known as familial chylomicronemia syndrome, is caused by homozygous or compound heterozygous pathogenic variants in the five canonical genes. Polygenic hypertriglyceridemia, also known as multifactorial chylomicronemia syndrome in extreme cases of hypertriglyceridemia, is caused by heterozygous pathogenic genetic variants with variable penetrance affecting the canonical genes, and a set of common non-pathogenic genetic variants (polymorphisms, using the former nomenclature) with well-established association with elevated triglyceride levels. We further address recent progress in triglyceride-lowering treatments. Understanding the genetic basis of hypertriglyceridemia opens new translational opportunities in the scope of genetic screening and the development of novel therapies.<\/jats:p>","DOI":"10.3390\/genes15020190","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T07:49:47Z","timestamp":1706600987000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Understanding Hypertriglyceridemia: Integrating Genetic Insights"],"prefix":"10.3390","volume":"15","author":[{"given":"Mara","family":"Alves","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5043-8997","authenticated-orcid":false,"given":"Francisco","family":"Laranjeira","sequence":"additional","affiliation":[{"name":"CGM\u2014Centro de Gen\u00e9tica M\u00e9dica Jacinto de Magalh\u00e3es, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio (CHUdSA), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-346 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-9018","authenticated-orcid":false,"given":"Georgina","family":"Correia-da-Silva","sequence":"additional","affiliation":[{"name":"UCIBIO Applied Molecular Biosciences Unit and Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.5543\/tkda.2022.98544","article-title":"Genetic Variants Associated with Severe Hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE","volume":"51","author":"Abedi","year":"2023","journal-title":"Turk. 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