Association of Trp64Arg polymorphism of the β3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity

Endo, Kazue; Yanagi, Hisako; Hirano, Chiaki; Hamaguchi, Hideo; Tsuchiya, Shigeru; Tomura, Shigeo

doi:10.1038/sj.ijo.0801177

Cited by 82 publications

(73 citation statements)

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“…We found that a significantly higher percentage (37%) of middleaged Korean obese women had the Trp64Arg polymorphism when compared to non-obese women (19%). These results together with recent findings in Pima Indians (5), Mexicans (21), Japanese (22), Chinese (23), Finns (6), and Caucasians (7) suggest that this polymorphism for the ␤3-adrenergic receptor gene mutation may be involved in a genetic predisposition for obesity in Korean middle-aged women. However, some other previous studies have not supported an associa- Values are number (%).…”

Section: Discussionmentioning

confidence: 64%

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: Discussionmentioning

confidence: 64%

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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“…The higher BW was due to increased accumulation of BF, that is, children with Arg64 allele were more obese than the children without this allele. Endo et al (2000) also found that BMI of Japanese children with the Arg64Arg or Trp64Arg genotypes was significantly higher than in those with the Trp64Trp genotype, so the polymorphism of the 3-BAR gene is a genetic risk factor for obesity. In a recent Italian study (Strazullo et al, 2001), the role of Arg64 allele in the development of abdominal adiposity was suggested in adults.…”

Section: Discussionmentioning

confidence: 91%

“…Several studies have investigated the association of Trp64Arg polymorphism of the 3-BAR gene with obesity or weight gain, but the results are equivocal (Allison et al, 1998;Fujisawa et al, 1998). Some studies (Endo et al, 2000) showed that the frequency of this polymorphism in obese patients was significantly higher than in normal subjects and BMI was significantly higher in subjects with Arg64 allele than in those homozygous for the normal allele. Kadowaki et al reported higher BMI not only in homozygotes but also in heterozygotes compared to normal subjects (Kadowaki et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

The frequency of Trp64Arg polymorphism of the β3-adrenergic receptor gene in healthy and obese Hungarian children and its association with cardiovascular risk factors

et al. 2005

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Objective: To estimate the frequency of Arg64 allele of the b 3 -adrenergic receptor (3-BAR) gene in healthy (H) and obese (O) Hungarian children, and to look for possible associations between this polymorphism and some clinical and metabolic characteristics of obese children. Patients/methods: In all, 147 healthy (male: 68) and 295 obese (male: 168) children were examined. The average age of the children in the two groups was 12.471.7 vs 12.673.2, respectively. Exon 1 of 3-BAR was amplified by polymerase chain reaction and the fragments were digested with BstN1. In obese children, oral glucose tolerance test was carried out and blood pressure (BP) was checked. Results: The frequency of Trp64Arg polymorphism in normal and obese Hungarian children was similar (H vs O: n ¼ 14/9.5% vs n ¼ 35/11.8%). Obese children carrying the Arg64 allele (n ¼ 35, male: 23) were compared to randomly chosen, obese children without the Arg64 allele (n ¼ 35, male: 20). A significant difference was found between the body weight (81.2723.2 vs 75.6717.7 kg; mean7s.d.; Po0.01), body fat (38.873.9 vs 36.572.3%; mean7s.d.; Po0.05), mean fasting insulin levels (31.4716.7 vs 16.977.6 mIU/ml; Po0.001) and mean systolic BP values (125.2710.1 vs 114.578.3 mmHg; Po0.001) of the two obese groups. Conclusions: The frequency of Trp64Arg polymorphism was similar in Hungary as compared to other European countries. Although the prevalence of this polymorphism was similar in H and O children, the presence of Arg64 allele seems to be associated with increased adiposity, elevated systolic BP and higher fasting insulin levels.European Journal of Clinical Nutrition (2005) 59, 955-959.

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“…In humans, the beta-3 adrenergic receptor is predominantly expressed in visceral adipose tissue (Krief et al, 1993). Notably, the Arg allele of this SNP has been linked with increased BMI, adiposity and obesity in children (Arashiro et al, 2003;Endo et al, 2000;Erhardt et al, 2005;Ochoa et al, 2004;Park et al, 2005) supporting the evidence in adults Pierola et al, 2007), and the increased risk for obesity at this ADRB3 loci may be driven partly by an interaction effect of the PPARG SNP Pro12Ala Hsueh et al, 2001;Ochoa et al, 2004). Other studies in young children between the ages 4-10 years and in adolescents report no signifi cant effects of Trp64Arg variants on BMI, weight or height when this variant is examined in isolation (Cecil et al, 2007;Haworth et al, 2008a;Hinney et al, 1997;Kurokawa et al, 2003).…”

Section: Adrenergic Receptor Gene Variants -A Role In Polygenic Obesimentioning

confidence: 99%

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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The prevalence of childhood obesity is increasing in many countries and confers risks for early type 2 diabetes, cardiovascular disease and metabolic syndrome. In the presence of potent ' obesogenic ' environments not all children become obese, indicating the presence of susceptibility and resistance. Taking an energy balance approach, susceptibility could be mediated through a failure of appetite regulation leading to increased energy intake or via diminished energy expenditure. Evidence shows that heritability estimates for BMI and body fat are paralleled by similar coeffi cients for energy intake and preferences for dietary fat. Twin studies implicate weak satiety and enhanced food responsiveness as factors determining an increase in BMI. Single gene mutations, for example in the leptin receptor gene, that lead to extreme obesity appear to operate through appetite regulating mechanisms and the phenotypic response involves overconsumption and a failure to inhibit eating. Investigations of robustly characterized common gene variants of fat mass and obesity associated ( FTO ), peroxisome proliferator-activated receptor ( PPARG ) and melanocortin 4 receptor ( MC4R ) which contribute to variance in BMI also infl uence the variance in appetite factors such as measured energy intake, satiety responsiveness and the intake of palatable energy-dense food. A review of the evidence suggests that susceptibility to childhood obesity involving specifi c allelic variants of certain genes is mediated primarily through food consumption (appetite regulation) rather than through a decrease in activity-related energy expenditure. This conclusion has implications for early detection of susceptibility, and for prevention and management of childhood obesity.

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Association of Trp64Arg polymorphism of the β3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity

Cited by 82 publications

References 48 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

The frequency of Trp64Arg polymorphism of the β3-adrenergic receptor gene in healthy and obese Hungarian children and its association with cardiovascular risk factors

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

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