Identification of TUB as a novel candidate gene influencing body weight in humans

R. Shiri-Sverdlov, A. Custers, J.V. van Vliet-Ostaptchouk, P.J.J. van Gorp, P.J. Lindsey, J.H.O. van Tilburg, S. Zhernakova, E. Feskens, D.L. van der A, M.E. Dolle, T.W. van Haeften, B.P. Koeleman, M.H. Hofker, C. Wijmenga

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Abstract

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/m(2), 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/m(2)) from the combined cohort with 289 normal subjects (BMI <25 kg/m(2)) 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.
Original languageEnglish
Pages (from-to)385-389
JournalDiabetes
Volume55
Issue number2
DOIs
Publication statusPublished - 1 Jan 2006

Cite this

Shiri-Sverdlov, R., Custers, A., van Vliet-Ostaptchouk, J. V., van Gorp, P. J. J., Lindsey, P. J., van Tilburg, J. H. O., Zhernakova, S., Feskens, E., van der A, D. L., Dolle, M. E., van Haeften, T. W., Koeleman, B. P., Hofker, M. H., & Wijmenga, C. (2006). Identification of TUB as a novel candidate gene influencing body weight in humans. Diabetes, 55(2), 385-389. https://doi.org/10.2337/diabetes.55.02.06.db05-0997