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

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, excep...

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Bibliographic Details
Published in:The Application of Clinical Genetics
Main Authors: Senftleber, Ninna Karsbæk, Ramne, Stina, Moltke, Ida, Jørgensen, Marit Eika, Albrechtsen, Anders, Hansen, Torben, Andersen, Mette K.
Format: Article in Journal/Newspaper
Language:English
Published: 2023
Subjects:
cardiometabolic health
congenital sucrase-isomaltase deficiency
Greenland
Inuit
loss-of-function variants
sucrase-isomaltase
sucrose
Arctic
greenlander*
greenlandic
inuit
Online Access:https://curis.ku.dk/portal/da/publications/genetic-loss-of-sucraseisomaltase-function(3c6ae98d-a756-4a7a-b069-cdf081ef330d).html
https://doi.org/10.2147/TACG.S401712
https://curis.ku.dk/ws/files/361842795/TACG_401712_genetic_loss_of_sucrase_isomaltase_function_mechanisms_imp.pdf
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Summary: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 SI 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.

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