Methylation in 3' near region of GC gene and its association with the level of vitamin D binding protein and type 2 diabetes mellitus

Abstract

As the major vitamin D binding protein (DBP), the group-specific component (GC) plays an important role in the bioactivity of vitamin D. Abnormal expression of GC gene may be associated with vitamin D related disease, type 2 diabetes mellitus (T2DM). DNA methylation is an important regulator of gene expression. It has been reported that methylation in 3' untranslated region played a role in regulation of protein expression via interaction with miRNA. This study hypothesized that DNA methylation of 3' near region of GC gene (3'GC) might be associated with T2DM. The methylation status of the 3'GC was assessed with high resolution melt method. Logistic regression was applied to assess the risk of T2DM at different levels of 3'GC methylation. The results showed that methylation level of the 3'GC was higher in T2DM patients than in non-T2DM individuals (P=.038). There was a significant association between 3'GC methylation level and T2DM (adjusted OR 1.282; 95% CI 1.062-1.548; P=.01). The association was independent upon serum glucose and insulin (adjusted OR 1.561; 95% CI 1.083-2.249; P=.017). Furthermore, there was a positive correlation between methylation level and the level of DBP in T2DM patients (r=0.126, P=.036). The association was also significant after adjusting the potential impact of rs705117 (P=.044). Besides, a positive correlation between methylation level and the level of fasting serum insulin was observed in non-T2DM (r=0.101, P<.001). These results suggest that methylation status of the 3'GC is most likely associated with DBP expression, insulin secretion, and T2DM.

Keywords: DNA methylation; Group-specific component; Type 2 diabetes mellitus; Vitamin D; Vitamin D binding protein.