title: Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population.
abstract: alpha(1A)-adrenergic receptor (alpha(1A)-AR) regulates the cardiac and peripheral vascular system through sympathetic activation, and alpha(2A)-AR and alpha(2C)-AR subtypes are essential for presynaptic feedback regulation of catecholamine release from the central and peripheral sympathetic nerve. Genetic variations in each human alpha-AR subtype gene have been identified and have been implicated in hypertension and cardiovascular disease. It is not yet clear whether these genetic variations actually have an effect on sympatho-vagal modulation. The aim of the present study was to evaluate the relation between the five representative genetic polymorphisms of alpha-AR subtypes (Arg347Cys of alpha(1A)-AR; C-1291G, Asn251Lys, and DraI RFLP of alpha(2A)-AR; and Del322-325 of alpha(2C)-AR) and autonomic nervous system (ANS) function in young and healthy Japanese males. One hundred forty-nine subjects were genotyped for each alpha-AR polymorphism, and underwent evaluation of ANS function by power spectral analysis of heart rate variability (HRV) during supine rest and in a standing position. In a supine position, the alpha(1A)-AR 347Cys allele was significantly associated with lower HRV sympathetic index (normalized low frequency power [LF(%)] and LF:HF ratio) and higher HRV parasympathetic index [HF(%)]. Meanwhile, subjects with the alpha(2C)-AR Del322-325 allele had markedly higher LF(%) and LF:HF ratio and lower HF(%) than noncarriers. Thus, the alpha(1A)-AR and alpha(2C)-AR genetic variations influence sympatho-vagal balance even in young and healthy normotensive states, which could be postulated to constitute an intermediate phenotype for future pathological episodes of various ANS dysfunction-related diseases.
authors.affiliation: Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsunaga
authors.affiliation: Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan. yasuda2@tom.life.h.kyoto-u.ac.jp.|Diabetic Center, Tsunashimakai-Kosei Hospital, Himeji, 670-0074, Japan. yasuda2@tom.life.h.kyoto-u.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.affiliation: Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Yamamura
authors.affiliation: Laboratory of Applied Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Moritani
authors.affiliation: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.affiliation: Laboratory of Metabolism, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Kinsuke
authors.initials: K
authors.lastname: Tsuda
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D001341:Autonomic Nervous System / Q000502:physiology*; D014644:Genetic Variation / Q000502:physiology*; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011942:Receptors, Adrenergic, alpha / Q000235:genetics*
chemical_list: D011942:Receptors, Adrenergic, alpha