Rs12778366 single nucleotide polymorphism of Sirtuin 1 (SIRT1) and response to resveratrol supplementation in patients with type 2 diabetes mellitus

Abstract

Resveratrol is a polyphenolic compound found in several plants, such as Polygonum cuspidatum roots, peanuts, berries and red grapes [S1, Online-Resource-1]. In preclinical studies, resveratrol has been shown to act as an activator of Sirtuin-1 (SIRT1), a NAD+ histone deacetylase, member of the sirtuins family, which plays a crucial role, among others, in glucose metabolism, nutrient sensing and inflammation shutdown [S2]. The potential role of SIRT1 variants has been investigated in various dysmetabolic and inflammatory diseases [S3]; moreover, the relationship between several single nucleotide polymorphisms (SNPs) and SIRT1 expression has recently been explored [S4–S7]. The effects of resveratrol in humans are controversial [S8], probably due to the unfavorable pharmacokinetics (such as low bioavailability, influenced by food matrix and gut microbiota) and the lack of well-defined pharmacodynamics [1, S9–S12]. We recently failed to demonstrate resveratrol-associated anti-inflammatory or insulin sensitizer effects in patients with type 2 diabetes mellitus (T2DM) [1]. Genetic background could play a major role in the individual response to resveratrol. Rs12778366, a SNP located in the promoter region of SIRT1 affecting its transcription [2], is one of the few SNPs studied after resveratrol supplementation with a potential impact in glucose metabolism [3, 4]. However, contrasting results have been reported on its role on metabolic and inflammatory outcomes [S13–S14]; moreover, whether the variant allele (C) enhances or reduces SIRT1 activity is still debated. We aimed to evaluate the impact of rs12778366 SNP on the response to resveratrol supplementation in T2DM patients.