Association of C825T polymorphism of G protein ?3 subunit with the autonomic nervous system in young healthy Japanese individuals

Matsunaga, Tetsuro; Nagasumi, Kae; Yamamura, Tsubasa; Gu, Ning; Nishikino, Mariko; Ueda, Yukihiko; Moritani, Toshio; Aoki, Norihiko; Tsuda, Kinsuke; Yasuda, Koichiro

doi:10.1016/j.amjhyper.2004.11.008

Cited by 19 publications

(18 citation statements)

References 31 publications

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“…For example, Baumgart et al [21] found an almost twofold enhanced α2-adrenoceptor-mediated vasoconstriction in 825T allele carriers. In a recent study of 94 young, healthy Japanese men [22], the 825T allele carriers had a significantly higher sympathetic nervous system index and lower parasympathetic nervous system index compared to the CC carriers. Additionally, the C825T may have functional consequences for the stimulation/inhibition of lipolysis in adipocytes.…”

Section: Adipositymentioning

confidence: 91%

Update on G-protein polymorphisms in hypertension

Zhu

Wang²,

Lu³

et al. 2006

Current Science Inc

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The classic candidate gene approach continues to be the most prevalent tool in the search for the genetic basis of essential hypertension. With the list of candidate genes for this disorder steadily increasing, the pertussis toxin-sensitive inhibitory G protein (Gi) protein beta3 subunit (GNB3) gene has remained "sizzling," challenging the domination of the renin-angiotensin system. Is the genetic variability of GNB3 a causative factor underlying the pathogenesis of essential hypertension? Is the "functional" polymorphism, C825T, only "another" of the countless single nucleotide polymorphisms (SNP) for this disorder after all? As such, does its presence merely reinforce our confidence that essential hypertension is indeed polygenic? Should the C825T polymorphism be used in clinical practice and individualized antihypertensive treatment? Currently, there are still more questions than answers. In this review, in conjunction with our own research, we bring readers up to date on the latest developments of GNB3 polymorphisms in the field of hypertension.

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Section: Adipositymentioning

confidence: 91%

Update on G-protein polymorphisms in hypertension

Zhu

Wang²,

Lu³

et al. 2006

Current Science Inc

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“…Following the previous reports (Liao et al 1996(Liao et al , 1997Matsunaga et al 2005;Piccirillo et al 1996), a natural logarithmic transformation was used to normalize the distribution of HRV power spectral indices because these data showed a distribution skewed to the right. Differences in BMI, BP, and log-transformed values (ln) of HRV indices were evaluated by one-way ANOVA or Student's t-test where appropriate.…”

Section: Discussionmentioning

confidence: 99%

“…The R-R interval power spectral analysis procedures have been described previously (Matsunaga et al 2005;Nishikino et al 2006;Suzuki et al 2003;Yasuda et al 2006). Briefly, the ECG R-R interval data obtained from the CM5 lead were digitized at 1,000 Hz, and the derived R-R interval time series were then aligned in a 2-Hz sequence for power spectral analysis.…”

Section: Ecg R-r Interval Power Spectral Analysismentioning

confidence: 99%

Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population

et al. 2006

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a 1A -adrenergic receptor (a 1A -AR) regulates the cardiac and peripheral vascular system through sympathetic activation, and a 2A -AR and a 2C -AR subtypes are essential for presynaptic feedback regulation of catecholamine release from the central and peripheral sympathetic nerve. Genetic variations in each human a-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 a-AR subtypes (Arg347Cys of a 1A -AR; C-1291G, Asn251Lys, and DraI RFLP of a 2A -AR; and Del322-325 of a 2C -AR) and autonomic nervous system (ANS) function in young and healthy Japanese males. One hundred forty-nine subjects were genotyped for each a-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 a 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 a 2C -AR Del322-325 allele had markedly higher LF(%) and LF:HF ratio and lower HF(%) than noncarriers. Thus, the a 1A -AR and a 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.

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“…Recently, an association of the GNB3/C825T polymorphism with the autonomic nervous system was demonstrated in young healthy Japanese men (Matsunaga et al 2005). G-proteins play an important role along with the major autonomic neurotransmitter receptors in autonomic transmission (Schnabel and Bohm 1996;Kirstein and Insel 2004).…”

Section: Discussionmentioning

confidence: 99%

“…G-proteins play an important role along with the major autonomic neurotransmitter receptors in autonomic transmission (Schnabel and Bohm 1996;Kirstein and Insel 2004). Because the 825T allele of GNB3 is associated with enhanced G-protein activation , different functions in sympathetic and parasympathetic system activities may result from modification of G protein-coupled receptormediated signaling in the autonomic system (Matsunaga et al 2005). Therefore, the pathology of the C825T polymorphism may be an altered autonomic nervous system.…”

Section: Discussionmentioning

confidence: 99%

G-Protein .BETA.3 Subunit Gene Variant is Unlikely to Have a Significant Influence on Serum Uric Acid Level in Japanese Workers

Suwazono

Kobayashi

Uetani

et al. 2006

Tohoku J. Exp. Med.

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The C825T variant of the G-protein β 3 subunit (GNB3) gene has attracted renewed attention as a candidate gene for obesity, hypertension and hyperuricemia. The main role of G-protein is to translate signals from the cell surface into a cellular response. The 825T allele is associated with a splice variant of GNB3 protein and enhanced G-protein activation. We examined the relationship between this variant and the risk of hyperuricemia in Japanese workers. The study subjects were 1,452 men and 1,169 women selected from 3,834 men and 2,591 women in 1997. On the basis of common clinical criteria, hyperuricemia I was defined as serum uric acid 7.0 mg/dl in men and 6.0 mg/dl in women or taking antihyperuricemic medication. The hyperuricemia I group consisted of 186 men and 20 women and its control of 1,266 men and 1,149 women. Hyperuricemia II was defined as serum uric acid > 5.7 mg/dl (median) in men and 3.9 mg/dl (median) in women or taking antihyperuricemic medication. The hyperuricemic II group consisted of 684 men and 570 women and its control of 768 men and 599 women. To replicate previous significant results in young Caucasian men, we selected these criteria because the authors of the study in young Caucasian men adopted the median in their subjects as a cut-off. The statistical power was estimated as 99% based on the significant results in Caucasians. Genotype and allele distributions in men and women with hyperuricemia I and II were not significantly different from those in the corresponding control groups. Logistic regression analysis on hyperuricemia I and II, and multiple regression on serum uric acid level demonstrated no significant effect of the C825T genotype. Despite the sufficient statistical power, this study could not demonstrate the significant influence of C825T on hyperuricemia or serum uric acid. The targeting of this polymorphism is unlikely to be beneficial in the prevention of hyperuricemia in the general Japanese population.

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Association of C825T polymorphism of G protein ?3 subunit with the autonomic nervous system in young healthy Japanese individuals

Abstract: These observations suggested that GNB3 C825T polymorphism is associated with ANS in youth. These findings raise the possibility that individuals who are T allele carriers are at increased risk for developing hypertension in relation to ANS function.

Cited by 19 publications

References 31 publications

Update on G-protein polymorphisms in hypertension

Update on G-protein polymorphisms in hypertension

Alpha-adrenoceptor gene variants and autonomic nervous system function in a young healthy Japanese population

G-Protein .BETA.3 Subunit Gene Variant is Unlikely to Have a Significant Influence on Serum Uric Acid Level in Japanese Workers

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