Genetic, Epigenetic and Biological Effects of Zinc Transporter (SLC30A8) in Type 1 and Type 2 Diabetes

Zinc is essential for the proper storage, secretion and action of insulin, while solute carrier family 30 members (SLC30A8) transports Zinc from cytoplasm to insulin secretory granules in the pancreatic beta-cells. Accumulating genetic studies have demonstrated that the common single nucleotide polymorphisms in the SLC30A8 gene confer the risk susceptibility to type 2 diabetes. The rare loss-of-function variants in the gene, however, may have protective effects in the disease. SLC30A8 is highly expressed in the pancreas, particularly in the islets of Langerhans. Clinical investigations have implicated that SLC30A8 acts as a new antigenic target in the patients with type 1 diabetes. Biological experimental evidence has indicated that this gene expression at both mRNA and protein levels is down-regulated in diabetic pancreatic islets. Furthermore, epigenetic analysis showed that DNA methylation levels in the SLC30A8 gene are increased in type 2 diabetes patients, which complies with the decreased gene expression. In this review, biological relevance and bioinformatics of Zinc transport SLC30A8 are described. Genetic and epigenetic effects of the SLC30A8 gene in type 1 and type 2 diabetes are summarized. Further investigation of SLC30A8 interactions with Zinc and other functional partners is discussed.