Polymorphisms in GLIS3 and susceptibility to diabetes mellitus: A systematic review and meta-analysis

The transcription factor Gli-similar 3 (GLIS3) has an important role in the development, survival and proliferation of pancreatic beta-cells and insulin gene expression regulation. Accordingly, genome-wide association studies have shown GLIS3 gene confers risk to both type 1 and type 2 diabetes mellitus (DM). However, data on the association of individual GLIS3 polymorphisms with DM are still inconclusive. Thus, this systematic review and meta-analysis was aimed to scrutinize the potential association between GLIS3 polymorphisms and DM. A literature search was carried out in EMBASE and PubMed resources to find all studies that analyzed GLIS3 polymorphisms regarding susceptibility to DM. Following the eligibility criteria, 25 studies were included in this systematic review. Twelve of them had complete data available, allowing meta-analyses (T1DM: 3 studies with rs7020673 polymorphism and 3 with rs10758593; T2DM: 6 with rs7034200 polymorphism and 3 with rs7041847). The rs7020673 and rs10758593 polymorphisms were not associated with T1DM. Regarding T2DM studies, the rs7041847A and the rs7034200C alleles were associated with risk for T2DM (OR = 1.08, 95% CI 1.00–1.16 and OR = 1.17, 95% CI 1.09–1.26; considering the allele contrast model). In conclusion, GLIS3 rs7034200 and rs7041847 polymorphisms seem to confer risk for T2DM. Additional studies are needed to confirm whether GLIS3 polymorphisms are associated with DM.