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Pediatr Obes. 2019 Jun;14(6):e12504. doi: 10.1111/ijpo.12504. Epub 2019 Jan 18.

Association between UCP1, UCP2, and UCP3 gene polymorphisms with markers of adiposity in European adolescents: The HELENA study.

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PROFITH "PROmotingFITness and Healththroughphysicalactivity" researchgroup. Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain.
Department of Physiology, Faculty of Medicine, University of Granada, Granada, Spain.
Department of Ecology, Faculty of Sciences, University of Granada, Granada, Spain.
Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Public University of Navarra, Pamplona, Spain.
Department of Health Sciences, Public University of Navarra, Pamplona, Spain.
Department of Applied Science of Nutrition, CREA (Council for Agricultural Research and Economics)-Research Center for Food and Nutrition, Rome, Italy.
Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
Immunonutrition Group, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Madrid, Spain.
Departamento de Metabolismo y Nutrición, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain.
Departamento de Salud y Rendimiento humano, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), Madrid, Spain.
ImFine Research Group, Facultad de Ciencias de la Actividad Física y del Deporte-INEF, Universidad Politécnica de Madrid, Madrid, Spain.
Inserm, Institut Pasteur de Lille, Univ. Lille, UMR1167-RID-AGE-Risk factors and molecular determinants of aging-related diseases, Lille, France.
Dep. of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Huddinge, Sweden.



To examine the association between UCP1, UCP2, and UCP3 gene polymorphisms with adiposity markers in European adolescents and to test if there were gene interactions with objectively measured physical activity and adiposity.


A cross-sectional study that involves 1.057 European adolescents (12-18 years old) from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-Sectional Study. A total of 18 polymorphisms in UCP1, UCP2, and UCP3 genes were genotyped. We measured weight, height, waist, and hip circumferences and triceps and subscapular skinfold thickness. Physical activity was objectively measured by accelerometry during 7 days.


The C allele of the UCP1 rs6536991 polymorphism was associated with a lower risk of overweight (odds ratio [OR]: T/C + C/C vs T/T) = 0.72; 95% confidence interval [CI]: 0.53-0.98; P = 0.034; false discovery rate [FDR] = 0.048). There was a significant interaction between UCP1 rs2071415 polymorphism and physical activity with waist-to-hip ratio (P = 0.006; FDR = 0.026). Adolescents who did not meet the physical activity recommendations (less than 60 min/day of moderate to vigorous physical activity) and carrying the C/C genotype had higher waist-to-hip ratio (+ 0.067; 95% CI, 0.028-0.106; P = 0.003), while no differences across genotypes were observed in adolescents meeting the recommendations.


Two UCP1 polymorphisms were associated with adiposity in European adolescents. Meeting the daily physical activity recommendations may overcome the effect of the UCP1 rs2071415 polymorphism on obesity-related traits.


Adolescents; brown adipose tissue; genetic susceptibility; uncoupling protein

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