Genetic Loss of Sucrase-Isomaltase Function: Mechanisms, Implications, and Future Perspectives.
Greenland
Inuit
cardiometabolic health
congenital sucrase-isomaltase deficiency
loss-of-function variants
sucrase-isomaltase
sucrose
Journal
The application of clinical genetics
ISSN: 1178-704X
Titre abrégé: Appl Clin Genet
Pays: New Zealand
ID NLM: 101579789
Informations de publication
Date de publication:
2023
2023
Historique:
received:
16
12
2022
accepted:
10
03
2023
medline:
31
3
2023
entrez:
30
3
2023
pubmed:
31
3
2023
Statut:
epublish
Résumé
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
Identifiants
pubmed: 36994449
doi: 10.2147/TACG.S401712
pii: 401712
pmc: PMC10041990
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
31-39Informations de copyright
© 2023 Senftleber et al.
Déclaration de conflit d'intérêts
NKS received funding from The Greenland Institute of Natural Resources (postdoctoral grant number 80.045) and The Greenlandic Research Council; held shares in Novo Nordisk AS, but sold in 2022. IM was supported by a Danish National Research Foundation Award (DNRF 143). MEJ received grants from the Independent Research Fund Denmark (grant number 1030-00363B); research grants from Boehringer Ingelheim, Novo Nordisk AS, and Sanofi Aventis, and holds shares in Novo Nordisk AS. TH was supported by a grant from Novo Nordisk Foundation (Grant number 0064142). The authors report no other conflicts of interest in this work
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