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

Moon, Seong-Su; Lee, Jung-Eun; Lee, Young-Sil; Kim, Su-Won; Jeoung, Nam Ho; Lee, In-Kyu; Kim, Jung-Guk

doi:10.1016/j.diabres.2011.09.035

« Previous Next »Diabetes Research and Clinical Practice
Volume 95, Issue 2 , Pages 230-236, February 2012

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

Seong-Su Moon
- Department of Internal medicine, Dongguk University School of Medicine, Gyeongju, South Korea
Jung-Eun Lee
- Division of Endocrinology, Department of Internal Medicine, CHA Gumi Medical Center, CHA University, Gumi, South Korea
Young-Sil Lee
- Department of Internal medicine, Dongguk University School of Medicine, Gyeongju, South Korea
Su-Won Kim
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea
- Department of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, South Korea
Nam Ho Jeoung
- Department of Fundamental Medical and Pharmaceutical Sciences, Catholic University of Daegu, Gyeongsan, South Korea
In-Kyu Lee
- Department of Endocrinology and Metabolism, Kyungpook National University Hospital, Daegu, South Korea
- WCU program, Kyungpook National University School of Medicine, Daegu, South Korea
- Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, South Korea
Jung-Guk Kim
- Department of Endocrinology and Metabolism, Kyungpook National University Hospital, Daegu, South Korea
- Corresponding author at: Department of Endocrinology and Metabolism, Kyungpook National University Hospital, 50 SAMDUK-2GA, Jungu, Daegu 700-721, South Korea. Tel.: +82 53 420 5566; fax: +82 53 426 2046.

Received 31 May 2011; received in revised form 20 September 2011; accepted 29 September 2011. published online 24 October 2011.

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.

Keywords: Pyruvate dehydrogenase kinase 4, Pyruvate dehydrogenase complex, Single nucleotide polymorphism, Type 2 diabetes, Metabolic syndrome