Rare MTNR1B variants causing diminished MT2 signalling associate with elevated HbA_1c levels but not with type 2 diabetes.

ABSTRACT:

Aims/hypothesis

An intronic variant (rs10830963) in MTNR1B (encoding the melatonin receptor type 2 [MT2]) has been shown to strongly associate with impaired glucose regulation and elevated type 2 diabetes prevalence. However, MTNR1B missense variants have shown conflicting results on type 2 diabetes. Thus, we aimed to gain further insights into the impact of MTNR1B coding variants on type 2 diabetes prevalence and related phenotypes.

Methods

We conducted a cross-sectional study, performing MTNR1B variant burden testing of glycaemic phenotypes (N=248,454, without diabetes), other cardiometabolic phenotypes (N=330,453) and type 2 diabetes prevalence (case-control study; N=263,739) in the UK Biobank. Similar burden testing with glycaemic phenotypes was performed in Danish Inter

SUBMITTER: Sorensen KV 

PROVIDER: S-EPMC12021717 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature