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  • Original Article
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Fat depot-specific mRNA expression of novel loci associated with waist–hip ratio

International Journal of Obesity volume 38, pages 120–125 (2014)Cite this article

Subjects

Abstract

Objective:

We hypothesized that genes within recently identified loci associated with waist–hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits.

Methods:

Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3 and GRB14) within these loci showing coincident cis-expression quantitative trait loci was measured in 222 paired samples of human visceral (vis) and subcutaneous (sc) AT. The relationship of mRNA expression levels with obesity-related quantitative traits was assessed by Pearson's correlation analyses. Multivariate linear relationships were assessed by generalized linear regression models.

Results:

Whereas only PIGC, ZNFR3 and STAB1 mRNA expression in sc AT correlated nominally with WHR (P<0.05, adjusted for age and sex), mRNA expression of all studied genes in at least one of the fat depots correlated significantly with vis and/or sc fat area (P ranging from 0.05 to 4.0 × 106, adjusted for age and sex). Consistently, the transcript levels of WARS, PIGC and GRB14 were nominally associated with body mass index (BMI) (P ranging from 0.02 to 9.2 × 105, adjusted for age and sex). Moreover, independent of sex, obesity and diabetes status, differential expression between vis and sc AT was observed for all tested genes (P<0.01). Finally, the rs10195252 T-allele was nominally associated with increased GRB14 sc mRNA expression (P=0.025 after adjusting for age, sex and BMI).

Conclusions:

Our data including the inter-depot variability of mRNA expression suggests that genes within the WHR-associated loci might be involved in the regulation of fat distribution.

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Acknowledgements

We thank all those who participated in the studies. We would like to acknowledge excellent technical assistance by Daniela Kox from the University of Leipzig and excellent clinical work by Edward Shang. This work was supported by grants from DFG (Deutsche Forschungsgemeinschaft—KO 3880/1-2, KL 2346, SFB-1052); German Diabetes Association (DDG; to J.B. and P.K.), LIFE (Leipzig Research Center for Civilization Diseases, Universität Leipzig. Leipzig Research Center for Civilization Diseases, Universität Leipzig), Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001 (N.K.), German Obesity Biomaterial Bank (FKZ: 01GI1128 to MB) and Boehringer Ingelheim Foundation (to D.S. and P.K.).

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Author notes

  1. D Schleinitz and N Klöting: These authors contributed equally to this work.

Authors and Affiliations

  1. Interdisciplinary Centre for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany

    D Schleinitz, J Breitfeld & P Kovacs

  2. Department of Internal Medicine, Neurology, and Dermatology, Clinic for Endocrinology and Nephrology, University Clinic of Leipzig, Leipzig, Germany

    N Klöting, A Dietrich, M Stumvoll & M Blüher

  3. IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany

    N Klöting, A Dietrich & M Stumvoll

  4. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    C M Lindgren & M I McCarthy

  5. Municipal Clinic Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, Germany

    M R Schön

  6. Municipal Clinic, Dresden, Germany

    T Lohmann & M Dreßler

  7. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK

    M I McCarthy

  8. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK

    M I McCarthy

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  1. D Schleinitz
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  2. N Klöting
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  10. M I McCarthy
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Corresponding authors

Correspondence to M Blüher or P Kovacs.

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The authors declare no conflict of interest.

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Schleinitz, D., Klöting, N., Lindgren, C. et al. Fat depot-specific mRNA expression of novel loci associated with waist–hip ratio. Int J Obes 38, 120–125 (2014). https://doi.org/10.1038/ijo.2013.56

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