TY - JOUR

T1 - Genetic Loss of Sucrase-Isomaltase Function

T2 - Mechanisms, Implications, and Future Perspectives

AU - Senftleber, Ninna Karsbæk

AU - Ramne, Stina

AU - Moltke, Ida

AU - Jørgensen, Marit Eika

AU - Albrechtsen, Anders

AU - Hansen, Torben

AU - Andersen, Mette K.

N1 - Publisher Copyright: © 2023 Senftleber et al.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - cardiometabolic health

KW - congenital sucrase-isomaltase deficiency

KW - Greenland

KW - Inuit

KW - loss-of-function variants

KW - sucrase-isomaltase

KW - sucrose

U2 - 10.2147/TACG.S401712

DO - 10.2147/TACG.S401712

M3 - Review

C2 - 36994449

AN - SCOPUS:85151714770

VL - 16

SP - 31

EP - 39

JO - Application of Clinical Genetics

JF - Application of Clinical Genetics

SN - 1178-704X

ER -