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Genetic variation in the vaspin gene affects circulating serum vaspin concentrations

International Journal of Obesity volume 37, pages 861–866 (2013)Cite this article

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Abstract

Objective:

Visceral adipose tissue-derived serine protease inhibitor (vaspin) is an adipokine potentially linking obesity, insulin resistance and type 2 diabetes. Here, we searched for genetic determinants that could explain the variability in serum vaspin concentrations.

Research Design and Methods:

First, we conducted a genome-wide association study (GWAS) for serum vaspin in the Sorbs cohort (N=826). Subsequently, 26 single-nucleotide polymorphisms (SNPs) covering genetic variation in the vaspin locus were genotyped in the Sorbs. In addition, we measured serum vaspin concentrations in 1806 samples from Augsburg/the Cooperative Health Research in the Region of Augsburg (KORA) for replication of the association signals. Finally, we conducted association analyses of vaspin SNPs with metabolic traits in the Sorbs (N=1013), KORA (N=1813) and a further cohort from Germany (Leipzig: N=1857).

Results:

Six SNPs mapping between serpinA1 and serpinA4, including the vaspin locus, on chromosome 14 reached P-values ⩽10−8 in the GWAS in the Sorbs. The fine mapping of variants within the vaspin locus in the Sorbs and subsequent replication in the KORA sample revealed several SNPs significantly associated with serum vaspin concentrations reaching P-values of up to 10−35. However, no significant association with type 2 diabetes or related traits was found in either cohort after the Bonferroni correction for multiple comparisons.

Conclusion:

Our data show that the variability in serum vaspin concentrations might be explained by its genetic variants.

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Acknowledgements

We thank all those who participated in the studies. We also acknowledge excellent technical assistance by Beate Enigk, Manuela Prellberg, Ines Müller and Janin Berndt. Data on glycaemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. This work was supported by grants from the Federal Ministry of Education and Research (BMBF), Boehringer Ingelheim Foundation (to PK and DS), Integrated Research and Treatment Center IFB Adiposity Diseases K7-37, 38, 39 (to YB) and Metarot position (to AT), Competence Network Obesity (FKZ 01GI0829), the Integrierte Verbünde der Medizinischen Genomforschung—NGFN-Plus (FKZ 01GI0827 and 01GS0823), Deutsche Forschungsgemeinschaft (DFG), the Clinical Research Group ‘Atherobesity’ KFO 152 (projects BL 833/1-1 to MB, Stu192/6-1 (MS), KO 3512/1-1 to AK and KO 3880/1-2 to PK, MB and JB), from the German Diabetes Association (to DS and PK), DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland; to MS, PK, MB and AT) and LIFE—Leipzig Research Center for Civilization Diseases, Universität Leipzig. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by means of the Free State of Saxony within the framework of the excellence initiative.

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Authors and Affiliations

  1. Department of Medicine, Medical Faculty, University of Leipzig, Leipzig, Germany

    J Breitfeld, A Tönjes, D Schleinitz, N Wiele, M Blüher, P Kovacs & M Stumvoll

  2. IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany

    A Tönjes, Y Böttcher & M Stumvoll

  3. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany

    C Marzi, H Grallert & T Illig

  4. German Center for Diabetes Research (DZD e. V.), Neuherberg, Germany

    C Marzi & H Grallert

  5. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University Munich, Munich, Germany

    C Brockhaus

  6. Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany

    C Brockhaus

  7. Institute of Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany

    W Rathmann

  8. Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany

    C Huth

  9. Medical School Hannover, Hannover Unified Biobank, Hannover, Germany

    T Illig

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  1. J Breitfeld
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Correspondence to P Kovacs.

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Supplementary Information accompanies the paper on International Journal of Obesity website

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Breitfeld, J., Tönjes, A., Böttcher, Y. et al. Genetic variation in the vaspin gene affects circulating serum vaspin concentrations. Int J Obes 37, 861–866 (2013). https://doi.org/10.1038/ijo.2012.133

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