Pathogenic monoallelic variants in GLIS3 increase type 2 diabetes risk and identify a subgroup of patients sensitive to sulfonylureas.
Sarah MeulebrouckVictoria ScherrerRaphaël BoutryBénédicte ToussaintEmmanuel VaillantAurélie DechaumeHélène LoiselleBeverley BalkauGuillaume CharpentierSylvia FrancMichel MarreMorgane BaronMartine VaxillaireMehdi DerhourhiMathilde BoisselPhillippe FroguelAmélie BonnefondPublished in: Diabetologia (2023)
Rare P/LP GLIS3 variants do contribute to type 2 diabetes risk. The variants located in the distal part of the protein could have a direct effect on its functional activity by impacting its transactivation domain, by homology with the mouse GLIS3 protein. Furthermore, rare P/LP GLIS3 variants seem to have a direct clinical effect on beta cell function, which could be improved by increasing insulin secretion via the use of sulfonylureas.
Keyphrases
- type diabetes
- copy number
- end stage renal disease
- cardiovascular disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- glycemic control
- protein protein
- prognostic factors
- binding protein
- insulin resistance
- peritoneal dialysis
- minimally invasive
- metabolic syndrome
- dna methylation
- adipose tissue
- genome wide
- patient reported outcomes
- patient reported
- study protocol