Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study

Erwin Reiling; Jana V van Vliet-Ostaptchouk; Esther van 't Riet; Timon W van Haeften; Pascal A Arp; Torben Hansen; Dennis Kremer; Marlous J Groenewoud; Els C van Hove; Johannes A Romijn; Jan W A Smit; Giel Nijpels; Robert J Heine; André G Uitterlinden; Oluf Pedersen; P Eline Slagboom; Johannes A Maassen; Marten H Hofker; Leen M 't Hart; Jacqueline M Dekker

doi:10.1038/ejhg.2009.4

Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study

Erwin Reiling, Jana V van Vliet-Ostaptchouk, Esther van 't Riet, Timon W van Haeften, Pascal A Arp, Torben Hansen, Dennis Kremer, Marlous J Groenewoud, Els C van Hove, Johannes A Romijn, Jan W A Smit, Giel Nijpels, Robert J Heine, André G Uitterlinden, Oluf Pedersen, P Eline Slagboom, Johannes A Maassen, Marten H Hofker, Leen M 't Hart, Jacqueline M Dekker

Department of Biomedical Sciences

9 Citations (Scopus)

Abstract

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.

Original language	English
Journal	European Journal of Human Genetics
Volume	17
Issue number	8
Pages (from-to)	1056-1062
Number of pages	6
ISSN	1018-4813
DOIs	https://doi.org/10.1038/ejhg.2009.4
Publication status	Published - 2009

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Reiling, E., van Vliet-Ostaptchouk, J. V., van 't Riet, E., van Haeften, T. W., Arp, P. A., Hansen, T., Kremer, D., Groenewoud, M. J., van Hove, E. C., Romijn, J. A., Smit, J. W. A., Nijpels, G., Heine, R. J., Uitterlinden, A. G., Pedersen, O., Slagboom, P. E., Maassen, J. A., Hofker, M. H., 't Hart, L. M., & Dekker, J. M. (2009). Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study. European Journal of Human Genetics, 17(8), 1056-1062. https://doi.org/10.1038/ejhg.2009.4

Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study. / Reiling, Erwin; van Vliet-Ostaptchouk, Jana V; van 't Riet, Esther et al.

In: European Journal of Human Genetics, Vol. 17, No. 8, 2009, p. 1056-1062.

Research output: Contribution to journal › Journal article › Research › peer-review

Reiling, E, van Vliet-Ostaptchouk, JV, van 't Riet, E, van Haeften, TW, Arp, PA, Hansen, T, Kremer, D, Groenewoud, MJ, van Hove, EC, Romijn, JA, Smit, JWA, Nijpels, G, Heine, RJ, Uitterlinden, AG, Pedersen, O, Slagboom, PE, Maassen, JA, Hofker, MH, 't Hart, LM & Dekker, JM 2009, 'Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study', European Journal of Human Genetics, vol. 17, no. 8, pp. 1056-1062. https://doi.org/10.1038/ejhg.2009.4

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abstract = "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.",

author = "Erwin Reiling and {van Vliet-Ostaptchouk}, {Jana V} and {van 't Riet}, Esther and {van Haeften}, {Timon W} and Arp, {Pascal A} and Torben Hansen and Dennis Kremer and Groenewoud, {Marlous J} and {van Hove}, {Els C} and Romijn, {Johannes A} and Smit, {Jan W A} and Giel Nijpels and Heine, {Robert J} and Uitterlinden, {Andr{\'e} G} and Oluf Pedersen and Slagboom, {P Eline} and Maassen, {Johannes A} and Hofker, {Marten H} and {'t Hart}, {Leen M} and Dekker, {Jacqueline M}",

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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

SN - 1018-4813

VL - 17

SP - 1056

EP - 1062

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 8

ER -

Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus: The DAMAGE study

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