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Diabetes 55:385-389, 2006
DOI: 10.2337/diabetes.55.02.06.db05-0997
© 2006 by the American Diabetes Association
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Brief Genetics Reports

Identification of TUB as a Novel Candidate Gene Influencing Body Weight in Humans

Ronit Shiri-Sverdlov1, Anne Custers1, Jana V. van Vliet-Ostaptchouk1, Patrick J.J. van Gorp1, Patrick J. Lindsey2, Jonathan H.O. van Tilburg3, Sasha Zhernakova3, Edith J.M. Feskens4, Daphne L. van der A4, Martijn E.T. Dollé5, Timon W. van Haeften3, Bobby P.C. Koeleman3, Marten H. Hofker1, and Cisca Wijmenga3

1 Department of Molecular Genetics, Maastricht University, Maastricht, the Netherlands
2 Department of Population Genetics, Maastricht University, Maastricht, the Netherlands
3 DBG-Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, the Netherlands
4 Centre for Nutrition and Health, National Institute of Public Health and the Environment (RIVM), Bilthoven, the Netherlands
5 Laboratory of Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, Bilthoven, the Netherlands

Address correspondence and reprint requests to Marten H. Hofker, Moleculaire Genetica (UNS50/11), Universiteit Maastricht, Universiteitssingel 50, Postbus 616, Maastricht 6200 MD, Netherlands. E-mail: m.hofker{at}gen.unimaas.nl

Key Words: SNP, single nucleotide polymorphism

Previously, we identified a locus on 11p influencing obesity in families with type 2 diabetes. Based on mouse studies, we selected TUB as a functional candidate gene and performed association studies to determine whether this controls obesity. We analyzed the genotypes of 13 single nucleotide polymorphisms (SNPs) around TUB in 492 unrelated type 2 diabetic patients with known BMI values. One SNP (rs1528133) was found to have a significant effect on BMI (1.54 kg/m2, P = 0.006). This association was confirmed in a population enriched for type 2 diabetes, using 750 individuals who were not selected for type 2 diabetes. Two SNPs in linkage disequilibrium with rs1528133 and mapping to the 3' end of TUB, rs2272382, and rs2272383 also affected BMI by 1.3 kg/m2 (P = 0.016 and P = 0.010, respectively). Combined analysis confirmed this association (P = 0.005 and P = 0.002, respectively). Moreover, comparing 349 obese subjects (BMI >30 kg/m2) from the combined cohort with 289 normal subjects (BMI <25 kg/m2) revealed that the protective alleles have a lower frequency in obese subjects (odds ratio 1.32 [95% CI 1.04–1.67], P = 0.022). Altogether, data from the tubby mouse as well as these data suggest that TUB could be an important factor in controlling the central regulation of body weight in humans.


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Copyright © 2006 by the American Diabetes Association.