Genetic variations of the bitter taste receptor TAS2R38 are associated with obesity and impact on single immune traits
Ortega FJ (1,2), Agüera Z (1,3), Sabater M (1,2), Moreno-Navarrete JM (1,2), Alonso-Ledesma I (1,2), Xifra G (2), Botas P (4), Delgado E (4), Jimenez-Murcia S (1,3), Fernández-García JC (1,5), Tinahones FJ (1,5), Baños RM (1,6), Botella C (1,7), de la Torre R (1,8,9), Frühbeck G (1,10), Rodriguez A (1,10), Estivill X (11), Casanueva F (1,12), Ricart W (1,2), Fernández-Aranda F (1,3), Fernández-Real JM (1,2).
(1) CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), and Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
(2) Service of Diabetes, Endocrinology and Nutrition (UDEN), and Institut d'Investigació Biomédica de Girona (IdIBGi), Girona, Spain.
(3) Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), and Department of Clinical Sciences, School of Medicine, University of Barcelona, (, ), Barcelona, Spain.
(4) Hospital Central de Asturias, Oviedo, Spain.
(5) Department of Diabetes, Endocrinology and Nutrition, Hospital Clínico Universitario Virgen de Victoria, Málaga, Spain.
(6) Department of Psychological, Personality, Evaluation and Treatment, University of Valencia, Valencia, Spain.
(7) Department of Basic Psychology, Clinic and Psychobiology, University Jaume I, (, ), Castelló, Spain.
(8) Department of Pharmacology, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
(9) Human Pharmacology and Clinical Neurosciences Research Group, Neuroscience Research Program, IMIM (Hospital del Mar Medical Research Institute), (, ), Barcelona, Spain.
(10) Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
(11) Center for Genomic Regulation (CRG) and CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
(12) Endocrine Division, Complejo Hospitalario U. de Santiago, Santiago de Compostela University, Santiago de Compostela, Spain.
Analyze changes in genetic variations affecting the taste receptor, type 2, member 38 (TAS2R38), identifying the interacting mechanism leading to obesity and potential associations with proteins partaking in innate immunity, such as surfactant protein D (SPD) and mannan-binding lectin (MBL).
METHODS AND RESULTS
We evaluated haplotypes of the bitter-taste receptor TAS2R38 in an identification sample of 210 women in different weight conditions, including anorexia nervosa and obesity. The association with SPD and MBL was tested in an independent sample picturing general population (n = 534).
The relationship with obesity was validated in an extended final sample of 1,319 participants. In the sample comprised of women in extreme weight conditions, increased obesity was identified in AVI/AVI subjects (OR = 2.5 [1.06-6.11], p = 0.035). In the sample picturing general population, increased SPD and MBL concentrations were found in non-smoking AVI-carriers. In this cohort, smoking and obesity blunted associations between TAS2R38 haplotypes and SPD and MBL.
In the extended sample, the association of AVI/AVI haplotypes with increased obesity was also identified (OR = 1.4 [0.99/1.85], p = 0.049), being more robust in subjects aged <40 years (OR = 1.9 [1.06/3.42], p = 0.031).
Current data reinforce the impact of TAS2R38 gene on phenotypic and clinical outputs affecting obesity, showing significant associations with extreme weight conditions (i.e. obesity and anorexia nervosa), and changes in both olfactory capacity and immune traits. This article is protected by copyright. All rights reserved.
CITATION Mol Nutr Food Res. 2016 Apr 5. doi: 10.1002/mnfr.201500804