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. © 2006 by the American Diabetes Association.
CITATION STYLE
Shiri-Sverdlov, R., Custers, A., Van Vliet-Ostaptchouk, J. V., Van Gorp, P. J. J., Lindsey, P. J., Van Tilburg, J. H. O., … 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
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