美国耶鲁医学院Arya Mani研究组宣布他们的最新研究揭示了CELA2A突变易导致早发性动脉粥样硬化和代谢综合征，并影响血浆胰岛素和血小板活化。 相关论文于2019年8月发表于国际顶尖学术期刊《自然—遗传学》杂志上。

该团队对与早发性动脉粥样硬化和代谢综合征极端表型患者有血缘关系的人，进行了全基因外显子序列分析。在基因编码的胰弹性蛋白酶糜蛋白酶样弹性蛋白酶家族成员2 (CELA2A)中确定了新的功能缺失基因突变 。研究人员进一步证明CELA2A是减少血小板超活化的循环酶，引起胰岛素分泌和退化，增加胰岛素敏感性。餐后人体内CELA2A血浆水平会上升，这与人类胰岛素水平相似。突变后的蛋白失去了这些功能，进而提供了对疾病机制的了解，并且表明CELA2A可能是一个引人注目的治疗靶标。

据了解，构成代谢综合征特征聚集的因素还未得到全面了解。
 

附：英文原文

Title: CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation

Author: Fatemehsadat Esteghamat, James S. Broughton, Emily Smith, Rebecca Cardone, Tarun Tyagi, Mateus Guerra, Andrs Szab, Nelson Ugwu, Mitra V. Mani, Bani Azari, Gerald Kayingo, Sunny Chung, Mohsen Fathzadeh, Ephraim Weiss, Jeffrey Bender, Shrikant Mane, Richard P. Lifton, Adebowale Adeniran, Michael H. Nathanson, Fred S. Gorelick, John Hwa, Mikls Sahin-Tth, Renata Belfort-DeAguiar, Richard G. Kibbey, Arya Mani

Issue&Volume: Volume 51 Issue 8

Abstract: Factors that underlie the clustering of metabolic syndrome traits are not fully known. We performed whole-exome sequence analysis in kindreds with extreme phenotypes of early-onset atherosclerosis and metabolic syndrome, and identified novel loss-of-function mutations in the gene encoding the pancreatic elastase chymotrypsin-like elastase family member 2A (CELA2A). We further show that CELA2A is a circulating enzyme that reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity. CELA2A plasma levels rise postprandially and parallel insulin levels in humans. Loss of these functions by the mutant proteins provides insight into disease mechanisms and suggests that CELA2A could be an attractive therapeutic target.

DOI: 10.1038/s41588-019-0470-3

Source:https://www.nature.com/articles/s41588-019-0470-3