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Diabetologia. 2008 Jan;51(1):54-61. Epub 2007 Oct 23.

TUB is a candidate gene for late-onset obesity in women.

Author information

1
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

Abstract

AIMS/HYPOTHESES:

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/INTERPRETATION:

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.

PMID:
17955208
DOI:
10.1007/s00125-007-0851-5
[Indexed for MEDLINE]

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