TY - JOUR
T1 - Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: the DAMAGE study
AU - Reiling, Erwin
AU - van Vliet-Ostaptchouk, Jana V.
AU - van 't Riet, Esther
AU - van Haeften, Timon W.
AU - Arp, Pascal A.
AU - Hansen, Torben
AU - Kremer, Dennis
AU - Groenewoud, Marlous J.
AU - van Hove, Els C.
AU - Romijn, Johannes A.
AU - Smit, Jan W. A.
AU - Nijpels, Giel
AU - Heine, Robert J.
AU - Uitterlinden, André G.
AU - Pedersen, Oluf
AU - Slagboom, P. Eline
AU - Maassen, Johannes A.
AU - Hofker, Marten H.
AU - 't Hart, Leen M.
AU - Dekker, Jacqueline M.
PY - 2009
Y1 - 2009
N2 - 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
AB - 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
U2 - https://doi.org/10.1038/ejhg.2009.4
DO - https://doi.org/10.1038/ejhg.2009.4
M3 - Article
C2 - 19209188
SN - 1018-4813
VL - 17
SP - 1056
EP - 1062
JO - European journal of human genetics
JF - European journal of human genetics
IS - 8
ER -