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03-11-2011 | Diabetes | Article

Critical regulator of glucose metabolism not linked to diabetes risk


Free abstract

MedWire News: Genetic variants in pyruvate dehydrogenase kinase 4 (PDK4) are not associated with Type 2 diabetes or with traits related to the metabolic syndrome, say researchers.

Although PDK4 is acknowledged to be critical for the regulation of both glucose and lipid metabolism, the authors say theirs is the first study to evaluate the association of PDK4 single nucleotide polymorphisms (SNPs) with diabetes.

"Moreover, no previous study has evaluated the relationship between PDK4 polymorphisms and other metabolic diseases such as obesity and metabolic syndrome," the team adds.

"PDK4 has recently emerged as a therapeutic target and candidate gene for Type 2 diabetes," say Jung-Guk Kim (Kyungpook National University, Daegu, South Korea) and colleagues.

"Four PDK isoenzymes (PDK1-4) have been identified in humans and rodents, one of which, PDK4, is highly expressed in heart, skeletal, muscle, liver, kidney, and pancreatic islets," they explain.

As reported in the journal Diabetes Research and Clinical Practice, the researchers examined the association of common PDK4 SNPs (rs10085637, rs3779478, rs2301630, rs12668651, and rs10247649) with Type 2 diabetes and the metabolic syndrome in 651 diabetes patients and 350 individuals without the condition.

There was no significant association between the polymorphisms and diabetes or any component of the metabolic syndrome including obesity, hyperglycemia, hypertension, or dyslipidemia.

The PDK4 ACAGC haplotype, constructed from the five SNPs studied, was significantly associated with the risk for diabetes, at an odds ratio of 0.65 versus the wild-type GTAGC haplotype.

However, the significance of this association was lost after correcting for multiple comparisons.

The authors say there may still be a positive association between these SNPs and diabetes or the metabolic syndrome, considering the limitations of the study and the crucial role of PDK4 in glucose and lipid metabolism.

"Further well-designed studies using a larger study population are required," conclude Kim et al.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Sally Robertson

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