The association of mitochondrial content with prevalent and incident type 2 diabetes.
BACKGROUND
It has been shown that mitochondrial DNA (mtDNA) content is associated with type 2 diabetes (T2D) and related traits. However, empirical data, often based on small samples, did not confirm this observation in all studies. Therefore, the role of mtDNA content in T2D remains elusive.


OBJECTIVE
In this study, we assessed the heritability of mtDNA content in buccal cells and analyzed the association of mtDNA content in blood with prevalent and incident T2D.


METHODS
mtDNA content from cells from buccal and blood samples was assessed using a real-time PCR-based assay. Heritability of mtDNA content was estimated in 391 twins from the Netherlands Twin Register. The association with prevalent T2D was tested in a case control study from The Netherlands (n = 329). Incident T2D was analyzed using prospective samples from Finland (n = 444) and The Netherlands (n = 238).


METHODS
We measured the heritability of mtDNA content and the association of mtDNA content in blood with prevalent and incident T2D.


RESULTS
A heritability of mtDNA content of 35% (19-48%) was estimated in the twin families. We did not observe evidence of an association between mtDNA content and prevalent or incident T2D and related traits. Furthermore, we observed a decline in mtDNA content with increasing age that was male specific (P = 0.001).


CONCLUSIONS
In this study, we show that mtDNA content has a heritability of 35% in Dutch twins. There is no association between mtDNA content in blood and prevalent or incident T2D and related traits in our study samples.
Leiden University Medical Center, Department of Molecular Cell Biology, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Erwin
E
Reiling
Charlotte
C
Ling
André G
AG
Uitterlinden
Esther
E
Van't Riet
Laura M C
LM
Welschen
Claes
C
Ladenvall
Peter
P
Almgren
Valeriya
V
Lyssenko
Giel
G
Nijpels
Els C
EC
van Hove
Johannes A
JA
Maassen
Eco J C
EJ
de Geus
Dorret I
DI
Boomsma
Jacqueline M
JM
Dekker
Leif
L
Groop
Gonneke
G
Willemsen
Leen M
LM
't Hart
D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012042:Registries; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004272:DNA, Mitochondrial