Polymorphisms of the TUB Gene Are Associated with Body Composition and Eating Behavior in Middle-Aged Women

Abstract

BackgroundThe TUB gene, encoding an evolutionary conserved protein, is highly expressed in the hypothalamus and might act as a transcription factor. Mutations in TUB cause late-onset obesity, insulin-resistance and neurosensory deficits in mice. An association of common variants in the TUB gene with body weight in humans has been reported.Methods/FindingsThe aim was to investigate the relationship of single nucleotide polymorphisms (SNPs) of the TUB gene (rs2272382, rs2272383 and rs1528133) with both anthropometry and self-reported macronutrient intake from a validated food frequency questionnaire. These associations were studied in a population-based, cross-sectional study of 1680 middle-aged Dutch women, using linear regression analysis. The minor allele C of the rs1528133 SNP was significantly associated with increased weight (+1.88 kg, P = 0.022) and BMI (+0.56 units, P = 0.05). Compared with non-carriers, both AG heterozygotes and AA homozygotes of the rs2272382 SNP derived less energy from fat (AG: −0.55±0.28%, P = 0.05, AA: −0.95±0.48%, P = 0.047). However, both genotypes were associated with an increased energy intake from carbohydrates (0.69±0.33%, P = 0.04 and 1.68±0.56%, P = 0.003, respectively), mainly because of a higher consumption of mono- and disaccharides. Both these SNPs, rs2272382 and rs1528133, were also associated with a higher glycemic load in the diet. The glycemic load was higher among those with AG and AA genotypes for the variant rs2272382 than among the wild types (+1.49 (95% CI: −0.27–3.24) and +3.89 (95% CI: 0.94–6.85) units, respectively). Carriers of the minor allele C of rs1528133 were associated with an increased glycemic load of 1.85 units compared with non-carriers.ConclusionsGenetic variation of the TUB gene was associated with both body composition and macronutrient intake, suggesting that TUB might influence eating behavior.

Individual Genetic Variations Related to Satiety and Appetite Control Increase Risk of Obesity in Preschool-Age Children in the STRONG Kids Program

“…In fact, one selected marker (TUB) still has limited information and replication, even though it has been associated with eating behavior and preference for carbohydrate intake [28] . The TUB gene encodes a bipartite transcription factor related to GPCRs that regulates gene expression after translocation from its membrane-bound location into the nucleus [24] .…”

“…The TUB gene encodes a transcription factor member of the G protein-coupled receptors (GPCRs) that regulates gene expression after translocation from its membrane-bound location into the nucleus [24] . TUB has been identified as a candidate gene for late-onset obesity development [25][26][27][28] and has been recently implicated in waist circumference regain after weight loss and the interindividual responses to dietary interventions [25] . However, the results of genetic association studies for the TUB gene are not consistent, and there are no data on the impact of TUB markers on obesity-related phenotypes in preschoolers.…”

Role of Fat Body Lipogenesis in Protection against the Effects of Caloric Overload in Drosophila

“…Loss of Tubby is correlated with obesity in mice, worms, and humans (43)(44)(45)(46)(47). Wandering third instar cg-GAL4; UAS-king-tubby i larvae were larger than stagematched controls when reared on the HSD (Fig.…”

Genetic and environmental influences on nutrient intake

“…Indeed, although genetic studies have been limited in their examination of specific food intake and appetite factors, studies have begun to shed light on how polymorphism of specific genetic loci is associated with specific macronutrient intake. For instance, the gene TUB has been associated with fat and carbohydrate intake; particularly, in women (van Vliet-Ostaptchouk et al 2008), MC4R has been associated with total energy, total fat, and protein intake (Qi et al 2008), and a single-nucleotide polymorphism at the FTO locus has been found to be related to fat intake in children (Timpson et al 2008). …”