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

H. Snieder, X. Wang, R. Shiri-Sverdlov, J. V. Van Vliet-Ostaptchouk, M. H. Hofker, U. Perks, T. D. Spector, S. D. O'Dell

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalDiabetologia
Volume51
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Association study
  • Central obesity
  • General obesity
  • Replication
  • TUB gene

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Snieder, H., Wang, X., Shiri-Sverdlov, R., Van Vliet-Ostaptchouk, J. V., Hofker, M. H., Perks, U., Spector, T. D., & O'Dell, S. D. (2008). TUB is a candidate gene for late-onset obesity in women. Diabetologia, 51(1), 54-61. https://doi.org/10.1007/s00125-007-0851-5