Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome.
OBJECTIVE
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.
Department of Internal medicine, Dongguk University School of Medicine, Gyeongju, South Korea. drmoonss@hanmail.net
Seong-Su
SS
Moon
Jung-Eun
JE
Lee
Young-Sil
YS
Lee
Su-Won
SW
Kim
Nam Ho
NH
Jeoung
In-Kyu
IK
Lee
Jung-Guk
JG
Kim
D000368:Aged; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics; D006973:Hypertension / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D056910:Republic of Korea / Q000453:epidemiology
C000631432:PDK4 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D017346:Protein Serine-Threonine Kinases