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The Association between Trp⁶⁴Arg Polymorphism of the ß₃-Adrenergic Receptor and Autonomic Nervous System Activity¹

Laboratories of Metabolism (N.S., T.A., H.T., K.T.) and Applied Physiology (T.M., H.U.), Kyoto University Graduate School of Human and Environmental Studies; the Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine (N.S., K.Y., T.A., H.T., Y.S.); and the Laboratory of Metabolism, Kyoto University Faculty of Integrated Human Studies (K.Y., K.T.), Kyoto 606-8501, Japan

Address all correspondence and requests for reprints to: Koichiro Yasuda, M.D., Ph.D., Laboratory of Metabolism, Kyoto University Faculty of Integrated Human Studies, Sakyo-ku, Kyoto 606-8501, Japan. E-mail: yasuda{at}metab.kuhp.kyoto-u.ac.jp

The ß₃-adrenergic receptor plays a significant role in the control of lipolysis and thermogenesis in brown adipose tissue through autonomic nervous system (ANS) activity. As the Trp⁶⁴Arg polymorphism of the ß₃-adrenergic receptor gene might affect ANS activity, we investigated the association of the polymorphism with ANS activity. The prevalence of the polymorphism was determined in 204 subjects. Ten normal homozygous, 10 heterozygous, and 1 variant homozygous subjects were examined for ANS activity during supine rest and standing by electrocardiogram R-R interval power spectral analysis. Subjects with the variant did not differ from subjects without the variant in body mass index, plasma glucose, plasma insulin, or family history of diabetes or obesity. The total power of heterozygotes at supine rest was lower than that of normal subjects (1124.6 ± 191.6 vs. 3029.8 ± 758.8 ms²; mean ± SE). With a postural change to standing, the parasympathetic and sympathetic nervous system activity indexes of heterozygotes showed a higher response than those of normal subjects (parasympathetic nervous system index, 0.10 ± 0.02 vs. 0.17 ± 0.02; sympathetic nervous system index, 10.55 ± 1.47 vs. 6.26 ± 1.09), and the difference in total power disappeared. These findings show that subjects with the variant, even the heterozygotes, had lower resting ANS activity than normal subjects.

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