并发急性胰腺炎或肝素后脂蛋白脂肪酶质量低的严重高甘油三酯血症的遗传和生化分析。

IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM
Endocrine journal Pub Date : 2024-05-23 Epub Date: 2024-02-09 DOI:10.1507/endocrj.EJ23-0438
Takashi Suzuki, Makoto Kurano, Akari Isono, Takuya Uchino, Yohei Sayama, Honami Tomomitsu, Daiki Mayumi, Ruriko Shibayama, Toru Sekiguchi, Naoki Edo, Kiyoko Uno-Eder, Kenji Uno, Koji Morita, Toshio Ishikawa, Kazuhisa Tsukamoto
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引用次数: 0

摘要

重度高甘油三酯血症是一种由遗传因素单独或与环境因素共同引起的病理状态,有时会导致急性胰腺炎(AP)。本研究对 4 例肥胖或糖尿病并发的高甘油三酯血症患者进行了外显子组测序和生化分析,这些患者均有 AP 病史或肝素后 LPL 质量下降。在一名有 AP 病史的患者中,导致 LMF1 无义突变的 SNP rs199953320 和导致脂蛋白 E2 的 APOE rs7412 均为杂合子形式。三名患者为 APOA5 rs2075291 的同卵双生型,一名为杂合型。对血清进行的酶联免疫吸附和 Western 印迹分析显示,无论是否存在 rs2075291,脂蛋白 A-V 都存在于不含脂蛋白的部分;此外,脂蛋白 A-V 的分子量因脂蛋白类别或不含脂蛋白的部分而异。脂质组学分析表明,血清中的鞘磷脂和多种甘油磷脂水平升高;然而,在对单个患者进行比较时,病例中各类磷脂的升高程度与总胆固醇和甘油三酯的升高程度并不一致。此外,出现 AP 的患者的磷脂酰胆碱、溶血磷脂酰肌醇和鞘磷脂水平往往高于未出现 AP 的患者,这表明这些磷脂可能有助于 AP 的发生。总之,本研究发现了一个新的致病基因 LMF1 突变,证实了多基因突变重叠与严重高甘油三酯血症之间的关联,并提示某些磷脂类别可能参与了 AP 的发病机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic and biochemical analysis of severe hypertriglyceridemia complicated with acute pancreatitis or with low post-heparin lipoprotein lipase mass.

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.

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来源期刊
Endocrine journal
Endocrine journal 医学-内分泌学与代谢
CiteScore
4.30
自引率
5.00%
发文量
224
审稿时长
1.5 months
期刊介绍: Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.
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