Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives

• Main Authors: Senftleber NK, Ramne S, Moltke I, Jørgensen ME, Albrechtsen A, Hansen T, Andersen MK
• Format: Article in Journal/Newspaper
• Language: English
• Published: Dove Medical Press 2023
• Subjects: sucrase-isomaltase; congenital sucrase-isomaltase deficiency; loss-of-function variants; cardiometabolic health; sucrose; greenland; inuit; Medicine (General); R5-920; Genetics; QH426-470; Arctic; Greenland; Ida; Moltke; Nuuk; Ramne; Tårnet; greenlander*; greenlandic
• Online Access: https://doaj.org/article/d93c1ecbd6f8484a8fb856ff32aa43c8

Ninna Karsbæk Senftleber,1,* Stina Ramne,2,* Ida Moltke,3 Marit Eika Jørgensen,1,4,5 Anders Albrechtsen,3 Torben Hansen,2 Mette K Andersen2 1Clinical Research, Copenhagen University Hospital – Steno Diabetes Center Copenhagen, Herlev, Denmark; 2Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 3Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark; 4Centre for Public Health in Greenland, National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; 5Steno Diabetes Center Greenland, Nuuk, Greenland*These authors contributed equally to this workCorrespondence: Mette K Andersen, University of Copenhagen, Blegdamsvej 3B, Mærsk Tårnet, 8. sal, 2200 København N., Copenhagen, Denmark, Tel [phone], Email [e-mail]: 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. ...