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Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

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Abstract

Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P=0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P=0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias.

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Acknowledgments

The FUSION study was funded by intramural funds from the NHGRI project OH95-C-N030, and by National Institutes of Health grants DK62370 and HG00376 to M.B. J.T. has been partially supported by the Academy of Finland (38387, 46558). R.N.B. was supported by NIH grants DK27619 and DK29867. R.M.W. is supported by the American Diabetes Association. K.L.M. is the recipient of a Burroughs Wellcome Career Award in the Biomedical Sciences. We thank Joanna Poulton for helpful comments.

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Authors and Affiliations

  1. Genome Technology Branch, National Human Genome Research Institute, Bethesda, MD, USA

    Erin C. Peck, Yong D. Suh, Peter S. Chines, Michael R. Erdos, Narisu Narisu, Sareena Enloe & Francis S. Collins

  2. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Anne U. Jackson, Laura J. Scott, Karen N. Conneely & Michael Boehnke

  3. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Richard M. Watanabe

  4. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Thomas A. Buchanan & Richard N. Bergman

  5. Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland

    Timo T. Valle & Jaakko Tuomilehto

  6. Department of Public Health, University of Helsinki, Helsinki, Finland

    Jaakko Tuomilehto

  7. South Ostrobothnia Central Hospital, Seinäjoki, Finland

    Jaakko Tuomilehto

  8. Department of Genetics, University of North Carolina, 4109-F Neurosciences Research Building, 103 Mason Farm Road, CB#7264, 27599-7264, Chapel Hill, NC, USA

    Karen L. Mohlke

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  1. Karen L. Mohlke
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  2. Anne U. Jackson
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  3. Laura J. Scott
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  4. Erin C. Peck
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  5. Yong D. Suh
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  6. Peter S. Chines
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  7. Richard M. Watanabe
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  8. Thomas A. Buchanan
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  9. Karen N. Conneely
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  10. Michael R. Erdos
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  11. Narisu Narisu
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  12. Sareena Enloe
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  13. Timo T. Valle
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  14. Jaakko Tuomilehto
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  15. Richard N. Bergman
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  16. Michael Boehnke
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  17. Francis S. Collins
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Correspondence to Karen L. Mohlke.

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Mohlke, K.L., Jackson, A.U., Scott, L.J. et al. Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns. Hum Genet 118, 245–254 (2005). https://doi.org/10.1007/s00439-005-0046-4

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