Gender-dependent miR-375 promoter methylation and the risk of type 2 diabetes

Abstract

Promoter DNA methylation may reflect the interaction between genetic background and environmental factors in the development of metabolic disorders, including type 2 diabetes (T2D). As an epigenetic factor of T2D, miR-375 plays an important role in the functional accommodation of islet cells. In the present study, we investigated the association of promoter DNA methylation of the miR-375 gene with the risk of T2D. Using bisulfite pyrosequencing technology, the DNA methylation levels of eight CpG dinucleotides on the miR-375 promoter were measured in 48 T2D cases and 48 healthy controls. The majority of CpGs (with the exception of CpG7) had significantly higher methylation levels in women compared with those in men (P<0.05). The methylation levels of the eight CpGs were significantly correlated with each other (P<0.001). No significant association between miR-375 gene promoter methylation and the risk of T2D was identified (P=0.417). Similar results were observed in the breakdown analysis by gender (men, P=0.844; women, P=0.234). In addition, although a correlation between the CpG8 methylation level of miR-375 and total triglyceride level was identified in women (P=0.009), DNA methylation of the majority of CpGs in the miR-375 gene promoter was not associated with the clinical metabolic features of the individuals.