دورية أكاديمية
Genetic and biochemical analysis of severe hypertriglyceridemia complicated with acute pancreatitis or with low post-heparin lipoprotein lipase mass.
| العنوان: | Genetic and biochemical analysis of severe hypertriglyceridemia complicated with acute pancreatitis or with low post-heparin lipoprotein lipase mass. |
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| المؤلفون: | Suzuki T; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Kurano M; Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.; Endowed Chairs Department of Clinical Research Medicine, Teikyo University, Tokyo 173-8605, Japan., Isono A; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Uchino T; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Sayama Y; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Tomomitsu H; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Mayumi D; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Shibayama R; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Sekiguchi T; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Edo N; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Uno-Eder K; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan.; Teikyo Academic Research Center, Teikyo University, Tokyo 173-8605, Japan., Uno K; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Morita K; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Ishikawa T; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan., Tsukamoto K; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo 173-8605, Japan. |
| المصدر: | Endocrine journal [Endocr J] 2024 May 23; Vol. 71 (5), pp. 447-460. Date of Electronic Publication: 2024 Feb 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Japan Endocrine Society Country of Publication: Japan NLM ID: 9313485 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1348-4540 (Electronic) Linking ISSN: 09188959 NLM ISO Abbreviation: Endocr J Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Tokyo : Japan Endocrine Society, [1993- |
| مواضيع طبية MeSH: | Pancreatitis*/genetics , Pancreatitis*/blood , Lipoprotein Lipase*/genetics , Lipoprotein Lipase*/blood , Hypertriglyceridemia*/genetics , Hypertriglyceridemia*/complications , Hypertriglyceridemia*/blood , Apolipoprotein A-V*/genetics, Humans ; Male ; Female ; Middle Aged ; Adult ; Apolipoproteins E/genetics ; Polymorphism, Single Nucleotide ; Exome Sequencing ; Obesity/complications ; Obesity/genetics ; Obesity/blood ; Acute Disease ; Triglycerides/blood ; Membrane Proteins |
| مستخلص: | Severe hypertriglyceridemia is a pathological condition caused by genetic factors alone or in combination with environmental factors, sometimes leading to acute pancreatitis (AP). In this study, exome sequencing and biochemical analyses were performed in 4 patients with hypertriglyceridemia complicated by obesity or diabetes with a history of AP or decreased post-heparin LPL mass. In a patient with a history of AP, SNP rs199953320 resulting in LMF1 nonsense mutation and APOE rs7412 causing apolipoprotein E2 were both found in heterozygous form. Three patients were homozygous for APOA5 rs2075291, and one was heterozygous. ELISA and Western blot analysis of the serum revealed the existence of apolipoprotein A-V in the lipoprotein-free fraction regardless of the presence or absence of rs2075291; furthermore, the molecular weight of apolipoprotein A-V was different depending on the class of lipoprotein or lipoprotein-free fraction. Lipidomics analysis showed increased serum levels of sphingomyelin and many classes of glycerophospholipid; however, when individual patients were compared, the degree of increase in each class of phospholipid among cases did not coincide with the increases seen in total cholesterol and triglycerides. Moreover, phosphatidylcholine, lysophosphatidylinositol, and sphingomyelin levels tended to be higher in patients who experienced AP than those who did not, suggesting that these phospholipids may contribute to the onset of AP. In summary, this study revealed a new disease-causing gene mutation in LMF1, confirmed an association between overlapping of multiple gene mutations and severe hypertriglyceridemia, and suggested that some classes of phospholipid may be involved in the pathogenesis of AP. |
| فهرسة مساهمة: | Keywords: Apolipoprotein A-V (ApoAV); Hypertriglyceridemia; Lipase maturation factor 1 (LMF1); Pancreatitis; Phospholipid |
| المشرفين على المادة: | EC 3.1.1.34 (Lipoprotein Lipase) 0 (Apolipoprotein A-V) 0 (LMF1 protein, human) 0 (APOA5 protein, human) 0 (Apolipoproteins E) 0 (ApoE protein, human) 0 (Triglycerides) EC 3.1.1.34 (LPL protein, human) 0 (Membrane Proteins) |
| تواريخ الأحداث: | Date Created: 20240212 Date Completed: 20240522 Latest Revision: 20240530 |
| رمز التحديث: | 20240530 |
| DOI: | 10.1507/endocrj.EJ23-0438 |
| PMID: | 38346769 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1348-4540 |
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| DOI: | 10.1507/endocrj.EJ23-0438 |