Correlation between Sirtuin 1 downregulation and reduced vitamin D receptor expression in patients with diabetic neuropathy

Aims: We aimed to analyse Sirtuin 1 (SIRT1) and Vitamin D receptor (VDR) expression levels in the peripheral blood of patients with type 2 diabetes (T2D), characterized for the presence of diabetic neuropathy (DN), and to evaluate possible genetic factors that could influence the VDR expression levels. Methods: Fifty-one participants with T2D, who underwent neurological assessment for DN were recruited. We quantified the mRNA levels of SIRT1 and VDR in peripheral blood mononuclear cells. Moreover, we analysed the methylation status and the rs2228570 genetic variant of VDR promoter. Results: Patients with DN (n = 32) showed lower expression of SIRT1 (pcorr=0.018) and VDR (pcorr=0.009), compared to those without DN. Furthermore, we observed a positive correlation between the mRNA levels of SIRT1 and VDR (p = 0.01). The expression levels of these genes negatively correlated with the score based on cardiovascular reflex tests (CARTs score). Moreover, the variant allele of rs2228570 in the VDR gene was associated with higher expression of this gene compared to the wild-type allele (p = 0.003). Conclusion: In patients with DN, both SIRT1 and VDR expression levels are reduced and interrelated. Low VDR expression levels could negatively affect SIRT1 transcription, thus influencing all the most pathogenetic pathways of DN regulated by this protein.