TUB is a candidate gene for late-onset obesity in women.
OBJECTIVE
We recently reported significant associations between BMI and three TUB single nucleotide polymorphisms (SNPs) in two Dutch cohorts enriched for type 2 diabetes. Here, we attempted a replication of these associations in a large population-based cohort of female twins comprehensively phenotyped for measures of general and central obesity.


METHODS
Two TUB SNPs (rs2272382, rs2272383) and a third (rs1528133), 22 kb distal to RIC3, were genotyped in 2694 Europid women from the St Thomas' UK Adult Twin Registry (Twins UK) (mean age +/- SD: 47.6 +/- 12.7 years; 42.8% postmenopausal). We explored the hypothesis that TUB is a candidate gene for late-onset obesity in humans through testing the interaction of the SNPs by menopausal status.


RESULTS
In the whole cohort, none of the three SNPs showed a significant main effect on measures of general or central obesity. However, for central obesity the rs2272382 SNP showed a significant interaction with menopausal status (p = 0.036). Postmenopausal women homozygous for the minor allele of rs2272382 showed significantly more general obesity (p = 0.022) and central obesity (p = 0.009) than carriers of the major allele. Differences (beta [95% CI]) between the two genotype groups were 0.92 kg/m2 (0.03-1.81) for BMI (p = 0.036), 2.73 cm (0.62-4.84) for waist circumference (p = 0.013) and 2.43% (0.27-4.60) for per cent central fat (p = 0.027). These associations were confirmed by a sibling transmission disequilibrium test for central obesity, waist circumference and per cent central fat.


CONCLUSIONS
We have replicated associations of TUB SNP rs2272382 with measures of general and central obesity in normal postmenopausal women. These findings confirm TUB as a candidate gene for late-onset obesity in humans.
Snieder
H
H
Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. h.snieder@epi.umcg.nl
Wang
X
X
Shiri-Sverdlov
R
R
van Vliet-Ostaptchouk
J V
JV
Hofker
M H
MH
Perks
U
U
Spector
T D
TD
O'Dell
S D
SD
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011506:Proteins / Q000235:genetics* / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; C508878:TUB protein, human