Novel association of SNP rs2297828 in PRDM16 gene with predisposition to type 2 diabetes

Transcriptional regulator PRD1-BF-1-RIZ1 homology (PR) domain containing protein-16 (PRDM16) has a fundamental function in maintaining energy homeostasis and regulating glucose and lipid metabolism, which are responsible for the development of type 2 diabetes (T2D). However, the impact of genetic variation of PRDM16 gene on T2D risk remains to be investigated. Thus, we evaluated the possible association between genetic variants within PRDM16 region and T2D development in Chinese individuals.A total of 427 T2D patients and 408 healthy controls were enrolled. Ten single-nucleotide variants across PRDM16 gene were screened with the SNaPshot assay. The effect of genotypes and alleles of different variant on the T2D risk was examined under diverse genetic models. The impact of genetic variant on promoter activity was determined using an in vitro luciferase reporter gene assay.Genotypic frequency of rs2297828 in the PRDM16 promoter region was significantly different between patients with T2D and controls (P = 0.004). The minor allele A of rs2297828 was potentially associated with a higher T2D susceptibility in a dominant model (AG + AA vs GG: OR = 1.54, 95 % CI: 1.12-1.12; P = 0.007), and the subjects with either an AA homozygote or an AG heterozygote displayed increased fasting blood levels of glucose and lipids. Reporter gene assays demonstrated that rs2297828 can influence the activity of the PRDM16 promoter.We firstly observed that PRDM16 variation might influence T2D occurrence, and rs2297828 might be a functional variant that can influence the expression of PRDM16.