Association of a Polymorphism in the β<sub>3</sub>-Adrenergic–Receptor Gene with Features of the Insulin Resistance Syndrome in Finns

Widén, Elisabeth; Lehto, Markku; Kanninen, Timo; Walston, Jeremy D.; Shuldiner, Alan R.; Groop, Leif

doi:10.1056/nejm199508103330604

Cited by 533 publications

(416 citation statements)

References 17 publications

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“…11,12 The receptor is expressed in visceral and subcutaneous fat tissue, but is more abundant and active in visceral tissue. 11 A missense change at codon 64 of this gene (Trp64Arg) has been identified and has been associated with measures of obesity, [12][13][14] weight gain, 15 insulin resistance 13 and type II diabetes. 12 In the current study, we examined the association between the codon 64 ADRB3 missense change and measures of weight and obesity among African-American breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

McKean‐Cowdin

Bernstein

et al. 2007

Int J Obes

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Objective: To determine if a missense change at codon 64 of ADRB3 (Trp64Arg), a candidate obesity gene, is associated with obesity and levels of subcutaneous or visceral fat in African-American breast cancer cases. Several observational studies have found that women, who are overweight or obese at the time of diagnosis, as well as those who gain weight after diagnosis, are at greater risk for breast cancer recurrence and death than non-overweight women. Design: Prospective cohort of breast cancer cases. Subjects: 219 African-American breast cancer patients participating in the Los Angeles component of the Health, Eating, Activity and Lifestyle Study. Measures: ADRB3 Trp64Arg genotype, measures of weight including body mass index (BMI), weight gain (weight 5 years before diagnosis compared with weight at 30 months after diagnosis), obesity (BMIX30 kg/m 2 ), waist/hip circumference and visceral or subcutaneous fat were determined by magnetic resonance imaging. Results: African-American women who were homozygous for the ADRB3 wild-type allele had significantly higher mean visceral fat levels than women who carried the variant (P ¼ 0.04), and were significantly more likely to be obese (odd ratios (OR) ¼ 2.1, 95% confidence interval (CI) ¼ 1.1-4.2). The association with obesity was most pronounced among women who were premenopausal (OR ¼ 4.8, 95% CI ¼ 1.3-18), who received chemotherapy for their breast cancer (OR ¼ 6.1, 95% CI ¼ 1.8-20), or who were not physically active (OR ¼ 3.9, 95% CI ¼ 1.5-9.7). Conclusion: The wild-type allele of the ADRB3 missense change was associated with measures of obesity in our sample of African-American women. The association was modified by menopausal status, history of chemotherapy and modest levels of physical activity. These results will need to be confirmed in an independent sample.

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Section: Introductionmentioning

confidence: 99%

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

McKean‐Cowdin

Bernstein

et al. 2007

Int J Obes

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“…Previous studies carried out in Japanese (Oizumi, Daimon, 2001) and in Finnish subjects (Widen, Lehto, 1995) reported that the Arg allele of the Trp53Arg polymorphism was associated with obesity. However, some studies failed to find such an association (Buettner et al , 1998, Gagnon et al , 1996, Gjesing, Andersen, 2008, Oeveren van-Dybicz et al , 2001.…”

Section: Discussionmentioning

confidence: 91%

“…For patients with schizophrenia, ANCOVA was also performed adding the chlorpromazine equivalent dose as a covariate to control for use of antipsychotics. Because the frequency of Arg/Arg homozygotes in the general population is low, we combined the heterozygotes and variant homozygotes into one group to assess the effect of the polymorphism on the degree of obesity, as in previous studies (Clement, Vaisse, 1995, Kurokawa et al , 2003, Widen, Lehto, 1995. Statistical analyses were performed using the Statistical Package for the Social Sciences version 11.0 (SPSS Japan, Tokyo, Japan).…”

Section: Discussionmentioning

confidence: 99%

“…Trp64Arg is a missense polymorphism in the β3-adrenoceptor (ADRB3) gene and is associated with lower lipolytic activities (Umekawa et al , 1999). The Arg allele of this polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease (Clement et al , 1995, Gjesing et al , 2008, Iwamoto et al , 2011, Oizumi et al , 2001, Widen et al , 1995.…”

Section: Introductionmentioning

confidence: 99%

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Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

Sasayama

Hori

Teraishi

et al. 2012

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Background: The β3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression.Methods: The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MDD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls. Conclusions: We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This 3 3 may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.

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“…42 The ADRA2A gene has no association with treatment efficacy and hypersalivation in Chinese schizophrenic patients receiving clozapine treatment, 43 but is associated with weight gain in Korean schizophrenic patients receiving olanzapine treatment. 44 The Arg347Cys (rs1048101) at ADRA1A gene and the Trp64Arg (rs4994) at ADRB3 gene, were examined by using a PstI RFLP 45 and a BstOI RFLP, 46 respectively. A MspI RFLP was used to discriminate the 1291C/G at the promoter region of the ADRA2A gene, as described elsewhere.…”

Section: Study Populationmentioning

confidence: 99%

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics

Lan

Loh

et al. 2008

Mol Psychiatry

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Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neurofuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.

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Association of a Polymorphism in the β₃-Adrenergic–Receptor Gene with Features of the Insulin Resistance Syndrome in Finns

Abstract: The Trp64Arg allele of the beta 3-adrenergic receptor is associated with abdominal obesity and resistance to insulin and may contribute to the early onset of NIDDM:

Cited by 533 publications

References 17 publications

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics

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Association of a Polymorphism in the β3-Adrenergic–Receptor Gene with Features of the Insulin Resistance Syndrome in Finns

Abstract: The Trp64Arg allele of the beta 3-adrenergic receptor is associated with abdominal obesity and resistance to insulin and may contribute to the early onset of NIDDM:

Cited by 533 publications

References 17 publications

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases

Possible impact of ADRB3 Trp64Arg polymorphism on BMI in patients with schizophrenia

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics

Contact Info

Product

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Association of a Polymorphism in the β₃-Adrenergic–Receptor Gene with Features of the Insulin Resistance Syndrome in Finns