Senftleber Ninna Karsbæk, Ramne Stina, Moltke Ida, Jørgensen Marit Eika, Albrechtsen Anders, Hansen Torben, Andersen Mette K
Clinical Research, Copenhagen University Hospital - Steno Diabetes Center Copenhagen, Herlev, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Appl Clin Genet. 2023 Mar 23;16:31-39. doi: 10.2147/TACG.S401712. eCollection 2023.
Genetic variants causing loss of sucrase-isomaltase (SI) function result in malabsorption of sucrose and starch components and the condition congenital sucrase-isomaltase deficiency (CSID). The identified genetic variants causing CSID are very rare in all surveyed populations around the globe, except the Arctic-specific c.273_274delAG loss-of-function (LoF) variant, which is common in the Greenlandic Inuit and other Arctic populations. In these populations, it is, therefore, possible to study people with loss of SI function in an unbiased way to elucidate the physiological function of SI, and investigate both short-term and long-term health effects of reduced small intestinal digestion of sucrose and starch. Importantly, a recent study of the LoF variant in Greenlanders reported that adult homozygous carriers have a markedly healthier metabolic profile. These findings indicate that SI inhibition could potentially improve metabolic health also in individuals not carrying the LoF variant, which is of great interest considering the massive number of individuals with obesity and type 2 diabetes worldwide. Therefore, the objectives of this review, are 1) to describe the biological role of SI, 2) to describe the metabolic impact of the Arctic LoF variant, 3) to reflect on potential mechanisms linking reduced SI function to metabolic health, and 4) to discuss what knowledge is necessary to properly evaluate whether SI inhibition is a potential therapeutic target for improving cardiometabolic health.
导致蔗糖酶 - 异麦芽糖酶（SI）功能丧失的基因变异会导致蔗糖和淀粉成分吸收不良，进而引发先天性蔗糖酶 - 异麦芽糖酶缺乏症（CSID）。除了北极地区特有的c.273_274delAG功能丧失（LoF）变异外，在全球所有被调查人群中，已鉴定出的导致CSID的基因变异都非常罕见，而这种变异在格陵兰因纽特人和其他北极人群中很常见。因此，在这些人群中，可以以无偏差的方式研究SI功能丧失的人群，以阐明SI的生理功能，并调查小肠对蔗糖和淀粉消化减少对短期和长期健康的影响。重要的是，最近一项关于格陵兰人LoF变异的研究报告称，成年纯合携带者的代谢状况明显更健康。这些发现表明，SI抑制可能也会改善非携带LoF变异个体的代谢健康，考虑到全球肥胖和2型糖尿病患者数量众多，这一点非常值得关注。因此，本综述的目的是：1）描述SI的生物学作用；2）描述北极LoF变异的代谢影响；3）思考将SI功能降低与代谢健康联系起来的潜在机制；4）讨论需要哪些知识来正确评估SI抑制是否是改善心脏代谢健康的潜在治疗靶点。
