Journal
DIABETES RESEARCH AND CLINICAL PRACTICE
Volume 95, Issue 2, Pages 230-236Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.diabres.2011.09.035
Keywords
Pyruvate dehydrogenase kinase 4; Pyruvate dehydrogenase complex; Single nucleotide polymorphism; Type 2 diabetes; Metabolic syndrome
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Funding
- BioMedical Research Institute
- Kyungpook National University Hospital
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0019514, R32-10064]
- Korea government (MEST) [20110001026]
- WCU (World Class University) through the National Research Foundation of Korea
- National Research Foundation of Korea [2010-0019514] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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