Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study.
Mitochondria play an important role in many processes, like glucose metabolism, fatty acid oxidation and ATP synthesis. In this study, we aimed to identify association of common polymorphisms in nuclear-encoded genes involved in mitochondrial protein synthesis and biogenesis with type II diabetes mellitus (T2DM) using a two-stage design. In the first stage, we analyzed 62 tagging single nucleotide polymorphisms (SNPs) in the Hoorn study (n=999 participants) covering all common variation in 13 biological candidate genes. These 13 candidate genes were selected from four clusters regarded essential for correct mitochondrial protein synthesis and biogenesis: aminoacyl tRNA synthetases, translation initiation factors, tRNA modifying enzymes and mitochondrial DNA transcription and replication. SNPs showing evidence for association with T2DM were measured in second stage genotyping (n=10164 participants). After a meta-analysis, only one SNP in SIRT4 (rs2522138) remained significant (P=0.01). Extending the second stage with samples from the Danish Steno Study (n=1220 participants) resulted in a common odds ratio (OR) of 0.92 (0.85-1.00), P=0.06. Moreover, in a large meta-analysis of three genome-wide association studies, this SNP was also not associated with T2DM (P=0.72). In conclusion, we did not find evidence for association of common variants in 13 nuclear-encoded mitochondrial proteins with T2DM.
Reiling
Erwin
E
Department of Molecular Cell Biology, Leiden University Medical Center, The Netherlands.
van Vliet-Ostaptchouk
Jana V
JV
van 't Riet
Esther
E
van Haeften
Timon W
TW
Arp
Pascal A
PA
Hansen
Torben
T
Kremer
Dennis
D
Groenewoud
Marlous J
MJ
van Hove
Els C
EC
Romijn
Johannes A
JA
Smit
Jan W A
JW
Nijpels
Giel
G
Heine
Robert J
RJ
Uitterlinden
André G
AG
Pedersen
Oluf
O
Slagboom
P Eline
PE
Maassen
Johannes A
JA
Hofker
Marten H
MH
't Hart
Leen M
LM
Dekker
Jacqueline M
JM
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000235:genetics*; D015331:Cohort Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D014176:Protein Biosynthesis / Q000235:genetics*