دورية أكاديمية
أعرض في EDS

The longitudinal triglyceride phenotype in heterozygotes with LPL pathogenic variants.

التفاصيل البيبلوغرافية
العنوان: The longitudinal triglyceride phenotype in heterozygotes with LPL pathogenic variants.
المؤلفون: Perera SD; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, Ontario N6A 5B7, Canada (Perera, Wang, McIntyre and Hegele); Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (Perera and Hegele)., Wang J; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, Ontario N6A 5B7, Canada (Perera, Wang, McIntyre and Hegele)., McIntyre AD; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, Ontario N6A 5B7, Canada (Perera, Wang, McIntyre and Hegele)., Dron JS; Center for Genomic Medicine, Massachusetts General Hopsital, Boston, Massachusetts, USA (Dron)., Hegele RA; Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 4288A-1151 Richmond Street North, London, Ontario N6A 5B7, Canada (Perera, Wang, McIntyre and Hegele); Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (Perera and Hegele); Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (Hegele). Electronic address: hegele@robarts.ca.
المصدر: Journal of clinical lipidology [J Clin Lipidol] 2023 Jan-Feb; Vol. 17 (1), pp. 87-93. Date of Electronic Publication: 2022 Nov 22.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 101300157 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1933-2874 (Print) Linking ISSN: 18764789 NLM ISO Abbreviation: J Clin Lipidol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Elsevier
مواضيع طبية MeSH: Hyperlipoproteinemia Type I*/genetics , Hypertriglyceridemia*/genetics, Humans ; Lipoprotein Lipase/genetics ; Heterozygote ; Triglycerides ; Phenotype
مستخلص: Background: Biallelic pathogenic variants in lipoprotein lipase (LPL) cause familial chylomicronemia syndrome with severe hypertriglyceridemia (HTG), defined as plasma triglycerides (TG) > 10 mmol/L (> 885 mg/dL). TG levels in individuals with one copy of a pathogenic LPL gene variant is less familiar; some assume that the phenotype is intermediate between homozygotes and controls.
Objective: We undertook an evaluation of the longitudinal TG phenotype of individuals heterozygous for pathogenic LPL variants.
Methods: Medically stable outpatients were evaluated based on having: (1) a single copy of a rare pathogenic LPL variant; and (2) serial fasting TG measurements obtained over > 1.5 years of follow-up.
Results: Fifteen patients with a single pathogenic LPL variant were followed for a mean of 10.3 years (range 1.5 to 30.3 years). TG levels varied widely both within and between patients. One patient had normal TG levels < 2.0 mmol/L (< 175 mg/dL) continuously, while four patients had at least one normal TG level. Most patients fluctuated between mild-to-moderate and severe HTG: five patients had only mild-to-moderate HTG, with TG levels ranging from 2.0 to 9.9 mmol/L (175 to 885 mg/dL), while 6 patients had at least one instance of severe HTG. Of the 203 total TG measurements from these patients, 14.8%, 67.0% and 18.2% were in the normal, mild-to-moderate and severe HTG ranges, respectively.
Conclusion: The heterozygous LPL deficient phenotype is highly variable both within and between patients. Heterozygosity confers susceptibility to a wide range of TG phenotypes, with severity likely depending on secondary factors.
Competing Interests: Declarations of Competing Interest R.A.H. reports consulting fees from Acasti, Aegerion, Akcea/Ionis, Amgen, Arrowhead, Boston Heart, HLS Therapeutics, Pfizer, Novartis, Regeneron, Sanofi and Ultragenyx. None of the other authors have any conflicts to report.
(Copyright © 2022. Published by Elsevier Inc.)
فهرسة مساهمة: Keywords: Complex trait; Familial chylomicronemia syndrome; Hyperlipoproteinemia type 1; Hyperlipoproteinemia type 5; Hypertriglyceridemia; Lipoprotein lipase deficiency; Multifactorial chylomicronemia syndrome; Next-generation DNA sequencing; Pathogenic variant
المشرفين على المادة: EC 3.1.1.34 (Lipoprotein Lipase)
0 (Triglycerides)
تواريخ الأحداث: Date Created: 20221208 Date Completed: 20230228 Latest Revision: 20230402
رمز التحديث: 20231215
DOI: 10.1016/j.jacl.2022.11.007
PMID: 36476373
قاعدة البيانات: MEDLINE
الوصف
تدمد:1933-2874
DOI:10.1016/j.jacl.2022.11.007