title: 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.
  
  
  METHODS
  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: 1] Department of Diabetes, Endocrinology and Nutrition. Institut d'Investigació Biomédica de Girona, Girona, Spain [2] CIBER Fisiopatologia de la Obesidad y la Nutrición, CIBEROBN (CB06/03), Instituto de Salud Carlos III, Girona, Spain.
authors: J M
authors: JM
authors: Fernández-Real
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authors: Corella
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authors: Goumidi
authors: J M
authors: JM
authors: Mercader
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authors: Valdés
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authors: Rojo Martínez
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authors: Ortega
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authors: Martinez-Larrad
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authors: Gómez-Zumaquero
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authors: Salas-Salvadó
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authors: Martinez González
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authors: Covas
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authors: Botas
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authors: Delgado
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authors: Cottel
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authors: Ferrieres
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authors: Amouyel
authors: W
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authors: Ricart
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authors: Ros
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authors: Meirhaeghe
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authors: Serrano-Rios
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authors: Soriguer
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authors: Estruch
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000235:genetics; D003430:Cross-Sectional Studies; D004041:Dietary Fats; D002149:Energy Intake; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013030:Spain; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D037021:Thyroid Hormone Receptors alpha