Genetic Variants in Melatonin Receptor Linked to Diabetes

Noting that previous genome-wide association studies had showed that common noncoding variants of MTNR1B were associated with an increased risk of type 2 diabetes, Amélie Bonnefond, from the Lille Pasteur Institute in France, and colleagues performed large-scale exon resequencing of the gene in 7,632 Europeans, of whom 2,186 had type 2 diabetes.

The researchers identified 40 non-synonymous variants associated with type 2 diabetes, of which 36 were very rare and significantly associated with increased diabetes risk (odds ratio [OR], 3.31). Fourteen of the variants were nonfunctional and rare, and four were very rare, resulting in complete loss-of-function. Among the very rare variants, those with partial or total loss-of-function were significantly associated with type 2 diabetes (OR, 5.67), whereas neutral variants were not associated with type 2 diabetes risk. The association of the four very rare, complete loss-of-function variants was verified in an independent group of 11,854 individuals (OR, 3.88).

"This study establishes a firm functional link between MTNR1B and type 2 diabetes risk," Bonnefond and colleagues conclude.

One of the study authors is an employee of Prognomix.

Abstract
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