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

^*Corresponding author for this work

Internal Medicine

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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.

Original language	English
Pages (from-to)	1056-1062
Number of pages	7
Journal	European Journal of Human Genetics
Volume	17
Issue number	8
DOIs	https://doi.org/10.1038/ejhg.2009.4
Publication status	Published - Aug 2009

Bibliographical note

Funding Information:
This study was supported by the Netherlands Organization for Scientific Research, ZonMW RIDE program and the Dutch Diabetes Research Foundation. The Danish study was supported by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP), the Danish Health Research Council, and The European Union (EUGENE2, Grant no. LSHM-CT-2004-512013). The authors would like to acknowledge the participants of all study cohorts for their cooperation.

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10.1038/ejhg.2009.4

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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

@article{e4d8664d14e344be84fc8b4dab9653d1,

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

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.",

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.}",

note = "Funding Information: This study was supported by the Netherlands Organization for Scientific Research, ZonMW RIDE program and the Dutch Diabetes Research Foundation. The Danish study was supported by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP), the Danish Health Research Council, and The European Union (EUGENE2, Grant no. LSHM-CT-2004-512013). The authors would like to acknowledge the participants of all study cohorts for their cooperation.",

year = "2009",

month = aug,

doi = "10.1038/ejhg.2009.4",

language = "English",

volume = "17",

pages = "1056--1062",

journal = "European Journal of Human Genetics",

issn = "1018-4813",

publisher = "Springer Nature",

number = "8",

}

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

TY - JOUR

T1 - Genetic association analysis of 13 nuclear-encoded mitochondrial candidate genes with type II diabetes mellitus

T2 - 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 - Funding Information: This study was supported by the Netherlands Organization for Scientific Research, ZonMW RIDE program and the Dutch Diabetes Research Foundation. The Danish study was supported by grants from the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LUCAMP), the Danish Health Research Council, and The European Union (EUGENE2, Grant no. LSHM-CT-2004-512013). The authors would like to acknowledge the participants of all study cohorts for their cooperation.

PY - 2009/8

Y1 - 2009/8

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.

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U2 - 10.1038/ejhg.2009.4

DO - 10.1038/ejhg.2009.4

M3 - Article

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AN - SCOPUS:67749137221

SN - 1018-4813

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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

Abstract

Bibliographical note

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