Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome

Abstract: Aims: Pyruvate dehydrogenase kinase 4 (PDK4) plays a crucial role in glucose utilization and lipid metabolism by regulating the pyruvate dehydrogenase complex (PDC) and is an emerging therapeutic target for type 2 diabetes. To date, no study has specifically examined the relationship between PDK4 gene polymorphisms and type 2 diabetes or metabolic syndrome. Methods: The association of common single nucleotide polymorphisms (SNPs) was examined in PDK4 [−208A/G (rs10085637), IVS3+192C/T (rs3779478), IVS6+31A/G (rs2301630), IVS7+514A/G (rs12668651), IVS10+75C/T (rs10247649)] with type 2 diabetes and metabolic syndrome in 651 Korean subjects with type 2 diabetes and 350 nondiabetic Korean subjects. The association of these SNPs with clinical parameters related to metabolic syndromes including obesity, hyperglycemia, hypertension, and dyslipidemia was also examined. Results: No significant association was found between the studied SNPs and type 2 diabetes, metabolic syndrome, or clinical parameters. The PDK4 gene haplotype ACAGC showed a modest association with type 2 diabetes. However, the significance of this association was lost after considering for multiple comparisons. Conclusions: PDK4 polymorphisms may not be associated with type 2 diabetes or metabolic syndrome. Further studies utilizing a larger study population are required to confirm these results. [Copyright &y& Elsevier]