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Association of SIRT1 gene variation with visceral obesity

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Abstract

The sirtuin SIRT1 is an important regulator of energy metabolism through its impact on glucose and lipid metabolism and therefore we tested the hypothesis that genetic variation in SIRT1 may have an effect on adiposity in a Belgian case/control association study. This study included 1,068 obese patients (BMI ≥ 30 kg/m2) from the outpatient obesity clinic and 313 lean controls (BMI between 18.5 and 25 kg/m2). Anthropometrics were assessed by classical methods and visceral (VFA), subcutaneous (SFA) and total abdominal (TFA) fat areas were determined by a CT scan. The extent of linkage disequilibrium in SIRT1 allowed us to reduce the number of SNPs to two, sufficient to cover the entire gene. The two tagSNPs (rs7069102 and rs3818292) were analyzed by LightSNiP assays in all subjects. Rs3818292 genotypes were similarly distributed in cases and controls, whereas rs7069102 was different for the additive (P = 0.007) and dominant (P = 0.01) model. The variant C-allele of rs7069102 reduced obesity risk with an OR of 0.74 (P = 0.025; 95% CI 0.57–0.96) under a dominant model. In obese male subjects, this variant allele was associated with increased waist circumference (P = 0.04), WHR (P = 0.02), TFA (P = 0.03) and VFA (P = 0.005) (dominant model; adjusted for age and BMI). Rs3818292 was related to VFA (P = 0.005; adjusted for age and BMI) in obese males while in obese women, no significant associations were detected. Our data suggest that genetic variation in SIRT1 increases the risk for obesity, and that SIRT1 genotype correlates with visceral obesity parameters in obese men.

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Acknowledgments

We thank J. Vertommen, M. Vinckx and P. Aerts for sampling handling. Financial support to this study was provided by Johnson & Johnson Pharmaceutical Research and Development, the University of Antwerp (NOI-BOF grant) and the Fund for Scientific Research (FWO) Flanders (research project) both to LVG and WVH. SB holds a predoctoral research grant from the Instituut voor de aanmoediging van innovatie door Wetenschap en Technologie (IWT) in Vlaanderen.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Center for Medical Genetics, University of Antwerp (UA), Universiteitsplein 1, Wilrijk, 2610, Antwerp, Belgium

    Armand V. Peeters, Sigri Beckers & Wim Van Hul

  2. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium

    An Verrijken, Ilse Mertens & Luc F. Van Gaal

  3. Department of Enabling Technologies Biology, Johnson & Johnson Pharmaceutical Research and Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium

    Peter Roevens & Pieter J. Peeters

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  1. Armand V. Peeters
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  2. Sigri Beckers
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  3. An Verrijken
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  4. Ilse Mertens
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Correspondence to Armand V. Peeters.

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A. V. Peeters and S. Beckers have contributed equally to this work.

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Peeters, A.V., Beckers, S., Verrijken, A. et al. Association of SIRT1 gene variation with visceral obesity. Hum Genet 124, 431–436 (2008). https://doi.org/10.1007/s00439-008-0567-8

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