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

N1 - Cited By (since 1996): 1Export Date: 4 November 2009Source: Scopus

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.European Journal of Human Genetics advance online publication, 11 February 2009; doi:10.1038/ejhg.2009.4.

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.European Journal of Human Genetics advance online publication, 11 February 2009; doi:10.1038/ejhg.2009.4.

U2 - 10.1038/ejhg.2009.4

DO - 10.1038/ejhg.2009.4

M3 - Journal article

C2 - 19209188

VL - 17

SP - 1056

EP - 1062

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 8

ER -