Identification of TUB as a novel candidate gene influencing body weight in humans.
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.
Shiri-Sverdlov
Ronit
R
Department of Molecular Genetics, Maastricht University, the Netherlands.
Custers
Anne
A
van Vliet-Ostaptchouk
Jana V
JV
van Gorp
Patrick J J
PJ
Lindsey
Patrick J
PJ
van Tilburg
Jonathan H O
JH
Zhernakova
Sasha
S
Feskens
Edith J M
EJ
van der A
Daphne L
DL
Dollé
Martijn E T
ME
van Haeften
Timon W
TW
Koeleman
Bobby P C
BP
Hofker
Marten H
MH
Wijmenga
Cisca
C
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; C508878:TUB protein, human