Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene-diet interactions.

Abstract

OBJECTIVE:

Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing.

DESIGN AND SUBJECTS:

THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial).

RESULTS:

The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass index (BMI) (P=0.042) in HCVR subjects. A more frequent THRA polymorphism (rs1568400) was associated with higher BMI in subjects from the population (P=0.00008 and P=0.05) after adjusting for several confounders. Rs1568400 was also strongly associated with fasting triglycerides (P dominant=3.99 × 10(-5)). In the same sample, 6 years later, age and sex-adjusted risk of developing obesity was significantly increased in GG homozygotes (odds ratio 2.93 (95% confidence interval, 1.05-6.95)). In contrast, no association between rs1568400 and BMI was observed in HCVR subjects, in whom obesity was highly prevalent. This might be explained by the presence of an interaction (P <0.001) among the rs1568400 variant, BMI and saturated fat intake. Only when saturated fat intake was high (>24.5 g d(-1)), GG carriers showed a significantly higher BMI than A carriers after controlling for energy intake and physical activity.

CONCLUSIONS:

THRA gene polymorphisms are associated with obesity development. This is a novel observation linking the THRA locus to metabolic phenotypes.

• Authors: J M Fernández-Real, D Corella, L Goumidi, J M Mercader, S Valdés, G Rojo Martínez, F Ortega, M-T Martinez-Larrad, J M Gómez-Zumaquero, J Salas-Salvadó, M A Martinez González, M I Covas, P Botas, E Delgado, D Cottel, J Ferrieres, P Amouyel, W Ricart, E Ros, A Meirhaeghe, M Serrano-Rios, F Soriguer, R Estruch
• Journal: International journal of obesity (2005) (Int J Obes (Lond)) Vol. 37 Issue 11 Pg. 1499-505 (Nov 2013) ISSN: 1476-5497 [Electronic] England
• PMID: 23399772 (Publication Type: Case Reports, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Thyroid Hormone Receptors alpha

Topics

• Adult
• Body Mass Index
• Cardiovascular Diseases (genetics)
• Cross-Sectional Studies
• Dietary Fats
• Energy Intake
• Female
• France
• Genetic Predisposition to Disease
• Heterozygote
• Humans
• Hypothyroidism (genetics, metabolism)
• Insulin Resistance (genetics)
• Male
• Middle Aged
• Obesity (etiology, genetics, metabolism)
• Polymorphism, Single Nucleotide
• Risk Factors
• Spain
• Thyroid Hormone Receptors alpha (genetics, metabolism)