The codon 64 polymorphism of the β3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients

Pulkkinen, Arto; Kareinen, Anu; Saarinen, Laura; Heikkinen, Sami; Lehto, Seppo; Laakso, Markku

doi:10.1016/s0026-0495(99)90218-4

Cited by 19 publications

(13 citation statements)

References 29 publications

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“…On the contrary, the Trp64Arg polymorphism of the ␤3-adrenergic receptor gene has not been related to insulin sensitivity (33,34) or WHR (20). Arii et al (35) and Hsueh et al (11) reported results similar to our observation as a lack of difference in body fat distribution in the abdomen between the ␤3-adrenergic receptor genotypes.…”

Section: Discussionsupporting

confidence: 85%

“…Thus, stimulation of ␤3-adrenergic receptors causes hydrolysis of triglyceride into fatty acids and glycerol by activation of hormone-sensitive lipase (19). The Trp64Arg polymorphism of the ␤3-adrenergic receptor gene has been associated with depression of lipolysis and morbid obesity in some (5,6,8), but not all (11,20) studies. To determine whether this relationship exists in Koreans, we related body composition as measured by CT, skinfold thickness and body circumferences to the ␤3-adrenergic receptor genotype.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Body Fat Distribution and Blood Lipid Profiles according to Trp64Arg Polymorphism for the .BETA.3-Adrenergic Receptor Gene in Korean Middle-Aged Women

Kim¹,

Lee²,

Lee³

et al. 2006

J Nutr Sci Vitaminol

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SummaryThe aim of this study was to determine whether there was an association between body fat distribution, blood lipid profiles, and ␤ 3 -adrenergic receptor gene polymorphism in Korean middle-aged women. Subjects were grouped according to BMI as obese ( Ն 25 BMI, n ϭ 95) or non-obese (BMI Ͻ 25, n ϭ 93). The Trp64Arg mutation of the ␤ 3 -adrenergic receptor gene was detected by PCR-RFLP. Skinfold thickness, body circumference, intra-abdominal fat area by CT, and blood lipid profiles were also measured. Data were compared using ANOVA, Bonferroni t -test, and Chi-square. Significance for statistical analyses were set at p Ͻ 0.05. In the obese group, 63.16% were Trp64Trp homozygotes and 36.84% were Trp64Arg heterozygotes, compared to 80.65% who were Trp64Trp homozygotes and 19.35% who were Trp64Arg heterozygotes in the non-obese group. These results indicated a significant ( 2 ϭ 4.943, p Ͻ 0.05) difference between the two groups. Frequency of the Arg64 allele in the obese group (16.84%) showed a significant ( 2 ϭ 4.185, p Ͻ 0.05) difference as compared to the non-obese group (9.68%). Skinfold thickness and body circumference of the Trp64Arg heterozygote group showed a consistent increase as compared to the Trp64Trp homozygote group. Visceral fat area and VSR of Trp64Arg heterozygote group showed a higher tendency than Trp64Trp homozygotes in the obese group, but these differences were not statistically significant. In conclusion, the Trp64Arg polymorphism of the ␤ 3 -adrenergic receptor gene is associated with obesity in middle-aged Korean women, but it is difficult to suggest the prominent association of the Trp64Arg polymorphism of the ␤ 3 -adrenergic receptor gene with prevalence of abdominal obesity or dyslipidemia in Korean middle-aged women. Key Words obesity, ␤ 3 -adrenergic receptor gene, Trp64Arg polymorphism, body fat distribution The obese phenotype is under the control of genetic and environmental influences. Much insight has been gained regarding obesity-related genetic factors ( 1 ), and the advent of advanced molecular biological techniques has accelerated the search for the specific genes influencing human obesity. Several candidate genes have been associated with energy expenditure, body fat distribution, and lipid metabolism ( 2 ). Among these genes, the ␤ 3 -adrenergic receptor gene regulates lipolysis in adipose tissue, and contributes to population variations in energy expenditure and body fat distribution ( 3 ). The ␤ 3 -adrenergic receptor is quite different from ␤ 1 and ␤ 2 receptor subtypes in that it is relatively resistant to desensitization and may maintain signaling during periods of sustained sympathetic stimulation ( 4 ). A missense mutation of the ␤ 3 -adrenergic receptor gene, results in replacement of tryptophan by arginine at codon 64 (Trp64Arg). This single nucleotide polymorphism (SNP) has been associated with morbid obesity and insulin resistance ( 5 ). The Trp64Arg polymorphism in the ␤ 3 -adrenergic receptor gene was shown to be associated decreased energy expenditure in P...

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Comparison of Body Fat Distribution and Blood Lipid Profiles according to Trp64Arg Polymorphism for the .BETA.3-Adrenergic Receptor Gene in Korean Middle-Aged Women

Kim¹,

Lee²,

Lee³

et al. 2006

J Nutr Sci Vitaminol

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“…However, these transgenic studies must be viewed critically because high levels of receptor overexpression have the potential to produce promiscuous receptor coupling to atypical signaling effectors, generating nonphysiological phenotypes. In any case, because most genetic work to date in cardiovascular disease has focused on the ␤ 1 -and ␤ 2 -receptor subtypes, and the handful of studies performed on ␤ 3 -adrenergic receptor polymorphisms have failed to show an association between the common ␤ 3 -adrenergic receptor Trp64Arg polymorphism and heart disease (91, 218,245,278,306,341), this review focuses on ␤ 1 -and ␤ 2 -adrenergic receptors.…”

Section: ␤-Adrenergic Receptorsmentioning

confidence: 99%

Adrenergic Signaling Polymorphisms and Their Impact on Cardiovascular Disease

Dorn

2010

Physiological Reviews

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This review examines the impact of recent discoveries defining personal genetics of adrenergic signaling polymorphisms on scientific discovery and medical practice related to cardiovascular diseases. The adrenergic system is the major regulator of minute-by-minute cardiovascular function. Inhibition of adrenergic signaling with pharmacological beta-adrenergic receptor antagonists (beta-blockers) is first-line therapy for heart failure and hypertension. Advances in pharmacology, molecular biology, and genetics of adrenergic signaling pathways have brought us to the point where personal genetic differences in adrenergic signaling factors are being assessed as determinants of risk or progression of cardiovascular disease. For a few polymorphisms, functional data generated in cell-based systems, genetic mouse models, and pharmacological provocation of human subjects are concordant with population studies that suggest altered risk of cardiovascular disease or therapeutic response to beta-blockers. For the majority of adrenergic pathway polymorphisms however, published data conflict, and the clinical relevance of individual genotyping remains uncertain. Here, the current state of laboratory and clinical evidence that adrenergic pathway polymorphisms can affect cardiovascular pathophysiology is comprehensively reviewed and compared, with a goal of placing these data in the broad context of potential clinical applicability.

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“…No association has been found between the Trp64Arg polymorphism and coronary artery disease [84], or the development of microvascular complications in diabetes [85,86]. Of interest, a study by Shihara et al [77] found an association between the Trp64Arg variant and decreased resting autonomic nervous system activity, as measured by electrocardiography and using R-R interval power spectral analysis.…”

Section: -Adrenergic Receptormentioning

confidence: 99%

Genetic polymorphisms of adrenergic receptors

Garland

Biaggioni

2001

Clinical Autonomic Research

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Recent advances in molecular biology have enhanced the understanding of adrenergic receptors. They have allowed the characterization of the several subtypes of adrenergic receptors expressed and have expanded the research about the potential physiologic functions they mediate. Furthermore, variant forms, or polymorphims, of the genes that code for these receptors are being identified. These genetic variants may or may not result in functional differences in the receptors they encode. There is obvious interest in determining the physiologic and clinical relevance of these polymorphisms. The purpose of this review is to describe these polymorphisms and the often contradictory literature pertaining to their clinical significance. Progress in this area is being made at a rapid pace. As the allele-disease relations become less equivocal, it might be possible to predict individual differences in susceptibility to a disease, disease prognosis, and response to treatment.

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The codon 64 polymorphism of the β3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients

Cited by 19 publications

References 29 publications

Comparison of Body Fat Distribution and Blood Lipid Profiles according to Trp64Arg Polymorphism for the .BETA.3-Adrenergic Receptor Gene in Korean Middle-Aged Women

Comparison of Body Fat Distribution and Blood Lipid Profiles according to Trp64Arg Polymorphism for the .BETA.3-Adrenergic Receptor Gene in Korean Middle-Aged Women

Adrenergic Signaling Polymorphisms and Their Impact on Cardiovascular Disease

Genetic polymorphisms of adrenergic receptors

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