Investigating the association between FOK1 polymorphism in the vitamin D receptor (VDR) gene and type 2 diabetes...

There is mounting evidence that suggests vitamin D insufficiency may have a role in the emergence of type 2 diabetes. Additionally, as VDR mediates the actions of vitamin D, variants in its sequence could have implications in this disease. One of these polymorphisms, Fok1 (rs2228570), has been demonstrated to generate changes in the receptor's structure, causing a shorter protein. The purpose of this research is to establish a potential association between the Fok1 polymorphism and DM2. To achieve such goal, a comprehensive study of this SNP was conducted using functional in-silico analysis and a systematic review with meta-analysis. Additionally, an examination of VDR gene expression in patients with diabetes compared to controls was performed in order to investigate possible differences in expression levels. Our expression analysis showed that VDR has no differential expression between these two groups. To study its functional consequences and stability, different tools were combined, without consistent results. Finally, our systematic review and meta-analysis showed that theFok1 variant was not significantly associated with the DM2 prevalence. This extensive analysis did not provide support for an association between the presence of Fok1 polymorphism and DM2. This result aligns with some previous studies but contrasts others that have reported both protective and risk factors.