The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus.

Autor:	Russ-Silsby J; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Patel KA; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Laver TW; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Hawkes G; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Johnson MB; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Wakeling MN; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Patil PP; The Society for the Rehabilitation of Crippled Children Narayana Health Children's Hospital, Mumbai, India., Hattersley AT; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Flanagan SE; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., Weedon MN; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K., De Franco E; Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, U.K.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2023 Nov 01; Vol. 72 (11), pp. 1729-1734.
DOI:	10.2337/db23-0498
Abstrakt:	ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and β-cell function. Recently, biallelic variants in ONECUT1 were reported as a cause of neonatal diabetes mellitus (NDM) in two subjects, and missense monoallelic variants were associated with type 2 diabetes and possibly maturity-onset diabetes of the young (MODY). Here we examine the role of ONECUT1 variants in NDM, MODY, and type 2 diabetes in large international cohorts of subjects with monogenic diabetes and >400,000 subjects from UK Biobank. We identified a biallelic frameshift ONECUT1 variant as the cause of NDM in one individual. However, we found no enrichment of missense or null ONECUT1 variants among 484 individuals clinically suspected of MODY, in whom all known genes had been excluded. Finally, using a rare variant burden test in the UK Biobank European cohort, we identified a significant association between heterozygous ONECUT1 null variants and type 2 diabetes (P = 0.006) but did not find an association between missense variants and type 2 diabetes. Our results confirm biallelic ONECUT1 variants as a cause of NDM and highlight monoallelic null variants as a risk factor for type 2 diabetes. These findings confirm the critical role of ONECUT1 in human β-cell function. (© 2023 by the American Diabetes Association.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu