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Synergistic effect of polymorphisms of uncoupling protein 1 and β3-adrenergic receptor genes on autonomic nervous system activity

International Journal of Obesity volume 25, pages 761–766 (2001)Cite this article

Abstract

OBJECTIVE: To investigate the association of the promoter region −3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the β3 adrenergic receptor (β3AR).

SUBJECTS: Three-hundred and forty-nine young (mean age 20.4±2.1 y old), healthy Japanese males.

MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability.

RESULTS: UCP1 or β3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of β3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2±50.3 vs 462.2±83.6 ms2; mean±s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG.

CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with β3AR polymorphism in decreasing sympathetic nervous system activity.

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Acknowledgements

This study was supported by grants-in-aids for scientific research from the Ministry of Education, Science, Sports and Culture (11839012, 10770569), health sciences research grants (Research on Human Genome and Gene Therapy, Choju Kagaku Sougou) from the Ministry of Health and Welfare, Japan, a grant from the Smoking Research Foundation and a grant for the ‘Research for the Future’ Program from the Japan Society for the Promotion of Science (JSPS RFTF97I00201). We thank Ms Kyoko Hishida and Mr Morisumi Ogido for technical assistance.

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Authors and Affiliations

  1. The Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan

    N Shihara, M Uno, T Adachi, K Nunoi & K Tsuda

  2. The Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    N Shihara, K Yasuda, T Adachi, Y Seino & Y Yamada

  3. The Laboratory of Metabolism, Faculty of Integrated Human Studies, Kyoto University, Kyoto, Japan

    K Yasuda & K Tsuda

  4. The Laboratory of Applied Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan

    T Moritani & H Ue

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Shihara, N., Yasuda, K., Moritani, T. et al. Synergistic effect of polymorphisms of uncoupling protein 1 and β3-adrenergic receptor genes on autonomic nervous system activity. Int J Obes 25, 761–766 (2001). https://doi.org/10.1038/sj.ijo.0801629

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