The beta3-adrenergic receptor Trp64Arg mutation is not associated with coronary artery disease

There is some evidence that the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. The objective of this cross-sectional study was to investigate the relationship between the Trp64Arg polymorphism and coronary artery disease (CAD). A total of 1,000 consecutive patients with angiographically confirmed CAD and 1,000 controls, carefully matched for age and sex, were genotyped for the Trp64Arg polymorphism by polymerase chain restriction and subsequent restriction fragment length polymorphism analysis. Among cases with CAD, 83.3% were wild-type Trp/Trp, 15.8% were heterozygotes, and 0.9% were homozygous Arg/Arg compared with 82.3%, 17.3%, and 0.4%, respectively, among controls (P = .27). The odds ratios for the presence of Trp/Arg and Arg/Arg in cases and controls were 0.90 (95% confidence interval [CI] 0.7 to 1.2; P = .40) and 2.2 (95% CI 0.7 to 7.2; P = .17), respectively. There was no effect modification by gender and atherogenic risk factors, including diabetes, hypercholesterolemia, hypertension, and smoking. Furthermore, there was no evidence of an association with premature disease onset (< 40 years) or extent of disease. In conclusion, the results of this study in a large sample of clinically well-characterized patients indicate that neither the Trp/Arg nor the Arg/Arg genotype represents a major risk factor for angiographically confirmed coronary artery disease.     

单纯肥胖与代谢综合征患者β3-肾上腺素能受体基因Trp64Arg突变的比较

目的　研究单纯肥胖和代谢综合征 (MS)患者 β3 肾上腺素能受体 (β3 AR)基因Trp6 4Arg突变的发生率及其性别、体脂含量和分布的差异。方法　选择单纯性肥胖症患者 2 95例和MS患者2 19例 ,并以 172例非肥胖者作为对照 ,进行 β3 AR基因Trp6 4Arg突变检测。并进一步比较基因突变的性别差异和对肥胖者按体重指数 (BMI)及腰围分组后的基因突变率。结果　MS组 β3 AR基因Trp6 4Arg突变频率高于单纯肥胖症组和对照组 ,主要表现在男性 (分别为 32 2 5 % ,2 1 0 1%和 19 91% ,P值均 <0 0 5 ) ,并高于本组女性 (32 2 5 %vs 2 3 4 6 % ,P <0 0 1)。进一步分组后发现 ,MS组中男性轻度肥胖者基因突变频率高于本组女性及单纯肥胖组男性轻度肥胖者 (分别为 32 83%vs 17 35 % ,P <0 0 5和 32 83%vs 2 0 4 1% ,P <0 0 5 )。男性腹部脂肪重度堆积者基因突变频率也以MS组高于单纯肥胖组 (35 71%vs 2 0 16 % ,P <0 0 5 )。结论　β3 AR基因Trp6 4Arg突变频率在体脂向心性分布较明显的MS组男性明显升高 ,可能是男性MS患者的重要遗传标志     

Association of amino acid variation (Trp64Arg) in the beta3-adrenergic receptor gene with bone mineral density

Background:   Recent studies have revealed that a mis-sense mutation replacing tryptophan with arginine at codon 64 (Trp64Arg) of the beta3-adrenergic receptor ( β3-AR ) gene was associated with insulin resistance in non-diabetic subjects and to earlier onset of non-insulin dependent diabetes mellitus. To analyze a possible involvement of β3-AR in bone metabolism, we investigated the association between bone mineral density (BMD) and the Trp64Arg polymorphism.
Methods:  A large cohort of Japanese postmenopausal women comprised the study population. The genotypic frequencies in this cohort were Trp/Trp, 61.8%; Trp/Arg, 33.2%; and Arg/Arg, 5.0%.
Results:  When the subjects were separated into two groups, one bearing at least one Trp allele at codon 64 (Trp/Trp and Trp/Arg) and the other with none (Arg/Arg), the former subjects had significantly higher Z scores for total-body BMD (mean ± SD, 0.432 ± 0.93 versus −0.135 ± 0.93; P  = 0.033).
Conclusions:   These data suggested an association between this single-nucleotide polymorphism (SNP) in the β3-AR gene and BMD, and therefore a possible involvement of the Arg allele (or the absence of Trp64) in postmenopausal osteoporosis among Japanese women.     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with hypertension in men with type 2 diabetes mellitus

A missense mutation of the beta3-adrenergic receptor gene (ADRB3) resulting in a tryptophan/arginine exchange at position 64 (Trp64Arg polymorphism) has recently been associated with greater capacity to gain weight, a low resting metabolic rate, higher blood pressure, and an early onset of type 2 diabetes. These findings prompted us to examine the relationship between this mutation, blood pressure, and vascular complications in German patients with type 2 diabetes. White patients with type 2 diabetes mellitus (n = 417) were enrolled in the study. The Trp64Arg polymorphism of the ADRB3 gene was detected by polymerase chain amplification and subsequent restriction digest with BstN I. Stepwise logistic regression analysis of the entire study population revealed a significant interaction between gender and genotype (P = .019). We therefore performed separate analyses for men and women. There was a significant relationship between hypertension and the ADRB3 Trp64Arg variant in men (P = .015), but not in women. Furthermore, blood pressure levels in male patients with the minor allele had higher blood pressure levels (P < .05), despite a significantly greater number of antihypertensive medications (P = .01). There was no association between ADRB3 genotype and vascular complications in these patients. In conclusion, our data are compatible with a contribution of this genetic variant of ADRB3 to hypertension in male patients with type 2 diabetes. Further studies will be needed to determine the role of this polymorphism as a predictor of hypertension or vascular complications in patients with type 2 diabetes.     

Trp64Arg polymorphism of the beta3-adrenergic receptor gene in pregnancy: association with mild gestational diabetes mellitus.

A missense mutation of the beta3-adrenergic receptor gene (Trp64Arg) has been associated with obesity and increased capacity to gain weight in nonpregnant populations. Furthermore, the mutation is a potential modifying factor in the etiology of impaired glucose tolerance and type 2 diabetes. We studied the relation of the beta3-adrenergic receptor genotype to glucose tolerance during pregnancy, a state of physiological insulin resistance. In 179 pregnant women (mean age, 28.5 +/- 0.4 yr), a 2-h oral glucose tolerance test was performed between gestational weeks 20 and 31. The beta3-adrenergic receptor genotype was assessed using restriction fragment length polymorphism. The frequency of the Arg64 allele was 9.15%. In women with mild gestational diabetes (n = 70), as defined by 60 min postload glucose values, the Trp64Arg genotype was more frequent than in women with normal glucose tolerance (n = 109; 26% vs. 11%; P = 0.01). Furthermore, the Trp64Arg polymorphism was associated with increased weight gain during pregnancy (baseline to gestational weeks 20-31) and increased postload glucose, insulin, and C peptide values during the oral glucose tolerance test. The results of the present study extend current knowledge about the association of the Trp64Arg beta3-adrenergic receptor polymorphism with glucose tolerance to a pregnant population. The association with mild gestational diabetes suggests that the impact of the polymorphism may be clinically important during pregnancy, a state of physiological insulin resistance.     

Association of Trp64Arg polymorphism of the beta3-adrenergic receptor gene and no association of Gln223Arg polymorphism of the leptin receptor gene in Japanese schoolchildren with obesity

OBJECTIVE: To investigate whether Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and Gln223Arg polymorphism of the leptin receptor (Ob-R) gene are associated with obesity in Japanese schoolchildren. DESIGN: Population study of participants from a rural town located within 50 km northeast of Tokyo based on school medical examinations. SUBJECTS: 553 Japanese schoolchildren (291 boys and 262 girls) who were 9-15 y old with a mean age of 11.9 +/- 1.8 y. MEASUREMENTS: DNA was extracted from whole blood and genotyped by PCR-RFLP. Height, weight and blood pressure were measured in school medical examinations. Total cholesterol, triglyceride and HDL-cholesterol concentrations were measured by an autoanalyzer. Obesity index, body mass index (BMI) and LDL-cholesterol concentration were calculated by the respective formulae. RESULTS: In Trp64Arg polymorphism of the beta3-AR gene, the number of obese subjects with Trp/Arg or Arg/Arg genotypes was significantly higher than that of the non-obese subjects (chi2=5.79, P=0.02). The obesity index of subjects with the Arg/Arg or Arg/Trp genotype was significantly higher than that of those with the Trp/Trp genotype (8.2 +/- 18.7% vs 4.5 +/- 15.8%, P=0.04). Moreover, after adjustments for age and gender, BMI of subjects with the Trp/Arg or Arg/Arg genotype was significantly higher than that of those with the Trp/Trp genotype (19.4 +/- 3.6 kg/m2 vs 18.9 +/- 3.2 kg/m2, P= 0.02). However, no significant differences were observed in the clinical characteristics among the genotype groups of the Ob-R gene. CONCLUSIONS: Trp64Arg polymorphism of the beta3-AR gene appears to be a genetic risk factor for obesity in Japanese children, but Gln223Arg polymorphism of the Ob-R gene does not appear to be associated with obesity.     

The Trp(64)Arg polymorphism of the beta(3)-adrenergic receptor gene is not associated with body weight or body mass index in Japanese: a longitudinal analysis

The beta(3)-adrenergic receptor (ADRB3) is expressed mainly in visceral adipose tissue and is thought to contribute to lipolysis and the delivery of free fatty acids to the portal vein. Although many studies have examined the relationship between the Trp(64)Arg mutation of ADRB3 and obesity, the results have been inconsistent. We examined the cross-sectional relationship of ADRB3 variants with indexes of obesity, and their longitudinal changes over 10 yr, in men and women, aged 40-69 yr, who were randomly selected from the Japanese rural population. The study considered both dietary energy intake and physical activity levels. Among the 746 participants, the genotype frequencies of the Trp(64)Trp, Trp(64)Arg, and Arg(64)Arg variants were 483, 224, and 39, respectively. The cross-sectional analysis showed no significant differences in height, weight, body mass index, blood pressure, serum total and high density lipoprotein cholesterols, and hemoglobin A(1c) among the genotype groups even after adjustments for gender, age, smoking, alcohol drinking, physical activity, and energy intake. No significant differences in the weight changes between the genotype groups were evident in the longitudinal analysis. We conclude that the Trp(64)Arg mutation of ADRB3 has little or no influence on either body weight or body mass index in the general Japanese population.     

Difficulty in losing weight by behavioral intervention for women with Trp64Arg polymorphism of the beta3-adrenergic receptor gene

OBJECTIVE: Trp64Arg mutation in the beta(3)-adrenergic receptor (beta(3)AR) gene is relatively common in Japanese people. However, it has not been clear whether persons with Trp64Arg mutation in the beta(3)AR gene tend to have obesity and difficulty in losing weight even with a restricted diet and exercise. We investigated the response of body weight and metabolic factors to behavioral intervention in Japanese women with Trp64Arg mutation in the beta(3)AR gene. DESIGN: A 3-month behavioral intervention study using a combination of diet and exercise programs. SUBJECTS: A total of 76 perimenopausal women with no clinical symptoms (age: 54.7+/-7.7 y, body mass index (BMI): 21.0-33.0 kg/m(2)). MEASUREMENTS: Anthropometric measurements (weight, height, body fat, waist circumference, hip circumference, skin fold, resting energy expenditure and blood pressure) and metabolic measurements (serum levels of cholesterol, triglyceride, phospholipid, nonesterified fatty acid, glucose, insulin and leptin) and determination of the beta(3)AR genotype by polymerase chain reaction followed by BstNI digestion. RESULTS: At the baseline of BMI, body weight, body fat, waist circumference, hip circumference, the arm skin fold, resting energy expenditure, or blood lipid and glucose profiles, there was no significant difference in participants with/without mutation of the beta(3)AR gene. The intervention yielded a body weight reduction in 69 and 48%, and induced a significant difference in weight loss (-0.74 and -0.01 kg) for women with wild-type and Trp64Arg mutation, respectively. Significant differences of anthropometric parameters were found in body weight, BMI, waist and hip circumferences and blood pressure of wild type by the intervention. However, women with Trp64Arg mutation did not show significant changes in these anthropometric parameters, except for hip circumference. A significant difference was found in high-density lipoprotein cholesterol (HDL-C) and in the low-density lipoprotein cholesterol/HDL-C ratio in both genotypes. CONCLUSION: The results of the present study suggest that the Trp64Arg mutation of the beta(3)AR gene is associated with difficulty in losing weight through behavioral intervention, although it is not related to obesity-related phenotypes and resting energy expenditure before the intervention.     

Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation

OBJECTIVE: To investigate the association between the Trp64Arg beta3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. DESIGN AND SUBJECT: Cross-sectional study in 1063 (476 men and 587 women) randomly selected from this population (aged: 18-68 years). MEASUREMENTS: Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism. RESULTS: Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060). We found gender-specific associations between the Trp64Arg mutation and obesity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 +/- 3.81 vs. 26.34 +/- 3.57 kg m-2, P=0.049) and total cholesterol (5.85 +/- 1.45 vs. 5.28 +/- 1.06 mmol L-1; P=0.011) compared with wild-type individuals. Logistic regression analysis, revealed that the risk of overweight was two times higher in male carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fasting glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables. For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men and women. However, after adjustment for covariates, these associations only remained statistically significant (P < 0.02) in women. Moreover, in women, a statistically significant interaction (P=0.026) between the LPL and the ADRB3 gene loci in determining BMI was found. Thus, the Arg64 allele was associated with a higher BMI only in H+/H+ women. CONCLUSIONS: The Trp64Arg mutation was associated with BMI and lipids in men. In women, an additional gene-gene interaction with the LPL-HindIII polymorphism may explain the results.     

Phenotypic characterization of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene in normal weight and obese subjects

Summary The beta₃-adrenergic receptor, located mainly in fat cells of visceral adipose tissue, is involved in the regulation of lipolysis and thermogenesis. Recently, a mutation in the corresponding gene resulting in the replacement of tryptophan by arginine in position 64 (Trp64Arg) has been demonstrated, which associated with obesity and metabolic complications of obesity. We have investigated whether this polymorphism is associated with changes in beta₃-adrenergic receptor function or clinical characteristics in 40 non-obese and 43 obese non-diabetic subjects who underwent elective abdominal surgery. The beta-adrenergic receptor gene polymorphism was examined by restriction-enzyme cleavage conformation. Beta₃-adrenergic receptor function was investigated by measuring lipolysis in isolated visceral white fat cells incubated with noradrenaline (natural ligand) or (CGP) 12177 (selective beta₃-agonist). No homozygotes for the mutation were found. The allelic frequency of Trp64Arg was similar in obese and non-obese subjects (9.4 and 12.5 %, respectively). In obese and non-obese subjects there was no change in body mass index, body fat distribution, fat cell size, fasting circulating levels of insulin, glucose or lipids, blood pressure or adipocyte lipolysis induced by noradrenaline or CGP 12177 when Trp64Arg heterozygotes were compared with Trp64 homozygotes. Our results suggest that the Trp64Arg mutation in its heterozygous form is not a major determinant of beta₃-adrenergic receptor function (when assessed by lipolysis in white adipose tissue) or of the pathophysiology of obesity. [Diabetologia (1996) 39: 857–860] Received: 21 February 1996 and in revised form: 22 March 1996     

Effects of intestinal fatty acid-binding protein gene Ala54Thr polymorphism and beta3-adrenergic receptor gene Trp64Arg polymorphism on insulin resistance and fasting plasma glucose in young to older Japanese men.

The present study was performed to investigate the effects of the intestinal fatty acid-binding protein (FABP2) gene Ala54Thr polymorphism and the beta(3)-adrenergic receptor (beta3AR) gene Trp64Arg polymorphism on body mass index (BMI), blood pressure, heart rate, glucose and lipid profiles, and serum leptin level in 196 young men aged 21 to 39 years, 186 older normoglycemic men (fasting plasma glucose [FPG] < 110 mg/dL) aged 40 to 65 years, and 122 older hyperglycemic men, including 77 type 2 diabetic patients. Genomic DNA was extracted from the peripheral blood, and these polymorphisms were assessed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. In the older groups, the beta3AR Arg64-allele frequency tended to be lower and the FABP2 Thr/Thr54 genotype frequency tended to be higher in hyperglycemic patients, although these differences did not reach statistical significance. Also, there were no significant differences in the genotype or allele frequency of either variant between the 27 hyperlipidemic and 204 normolipidemic subjects. In the younger group, there were no significant differences in any of the parameters measured between the genotypes of beta3AR or FABP2. In the older normoglycemic subjects, heart rate was significantly lower (P =.037) in beta3AR Arg64-positive subjects, and FPG was significantly higher in subjects with the FABP2 Thr/Thr genotype than the other genotypes (99.8 +/- 5.6 v 96.5 +/- 5.6 mg/dL, P =.010). In the older hyperglycemic group, the beta3AR Arg64-positive group had significantly lower high-density lipoprotein (HDL) cholesterol and free fatty acid (FFA) levels (P =.024 and P =.043, respectively). There were no synergistic effects of these 2 variants on any measured parameter, but only the FABP2 Thr/Thr genotype was related to a higher FPG in the older normoglycemic men. In conclusion, no major difference was associated with the beta3AR Trp64Arg or FABP2 Ala54Thr polymorphism in terms of type 2 diabetes or hyperlipidemia in young to older Japanese men. However, a slight but significant increase in FPG was observed in older Japanese men with the FABP2 Thr/Thr genotype.     

The association between Trp64Arg polymorphism of the beta3-adrenergic receptor and autonomic nervous system activity.

The beta3-adrenergic receptor plays a significant role in the control of lipolysis and thermogenesis in brown adipose tissue through autonomic nervous system (ANS) activity. As the Trp64Arg polymorphism of the beta3-adrenergic receptor gene might affect ANS activity, we investigated the association of the polymorphism with ANS activity. The prevalence of the polymorphism was determined in 204 subjects. Ten normal homozygous, 10 heterozygous, and 1 variant homozygous subjects were examined for ANS activity during supine rest and standing by electrocardiogram R-R interval power spectral analysis. Subjects with the variant did not differ from subjects without the variant in body mass index, plasma glucose, plasma insulin, or family history of diabetes or obesity. The total power of heterozygotes at supine rest was lower than that of normal subjects (1124.6 +/- 191.6 vs. 3029.8 +/- 758.8 ms2; mean +/- SE). With a postural change to standing, the parasympathetic and sympathetic nervous system activity indexes of heterozygotes showed a higher response than those of normal subjects (parasympathetic nervous system index, 0.10 +/- 0.02 vs. 0.17 +/- 0.02; sympathetic nervous system index, 10.55 +/- 1.47 vs. 6.26 +/- 1.09), and the difference in total power disappeared. These findings show that subjects with the variant, even the heterozygotes, had lower resting ANS activity than normal subjects.     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome

BACKGROUND: In regions such as Hong Kong, rapid economic development has led to lifestyle alterations characterized by increases in energy and fat intake and reduction in physical activity. These changes have been associated with a dramatic increase in the prevalence of diabetes and related diseases of the metabolic syndrome. OBJECTIVE: To investigate if a common polymorphism (Trp64Arg) of the beta3-adrenergic receptor gene, previously implicated as predisposing to type 2 diabetes mellitus or obesity in other populations, has a role in the apparent susceptibility of Hong Kong Chinese to diabetes and related disorders. METHOD: A PCR-based protocol was used to genotype 802 Southern Chinese subjects who were either healthy or had one or more of the metabolic disorders including diabetes, hypertension or dyslipidaemia. RESULTS: The frequencies of the mutant A allele (12.7%) and AA genotype (1.7%) did not differ, by the chi2 test, in any patient group with diabetes, hypertension or dyslipidaemia, alone or in combination, compared to healthy controls. Using the t-test in the 802 subjects, those carrying the mutant A allele had evidence of increased obesity with a significantly (all P<0.05) higher body mass index (BMI, kg/m2) and also lower HDL-cholesterol. BMI was also elevated in subjects with the A allele in the separate groups with diabetes, dyslipidaemia or hypertension. Stepwise multiple regression showed this polymorphism to be an independent predictor of BMI. CONCLUSION: These data do not support any direct involvement of the Trp64Arg polymorphism in the development of diabetes, hypertension or dyslipidaemia in Chinese subjects, but do suggest a relationship with obesity.     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with increased small dense low-density lipoprotein in a rural Japanese population: the Mima study

The presence of small dense low-density lipoprotein (sdLDL) is closely associated with an increased risk of developing coronary artery disease. The Trp64Arg polymorphism of the beta(3)-adrenergic receptor (beta(3)-AR) gene is a genetic marker for obesity-related traits. However, any possible association between this polymorphism and sdLDL profiles is unclear. The objective of this study is to investigate the effects of the polymorphism of the beta(3)-AR gene on LDL particle size and sdLDL in a rural Japanese population. Among 277 subjects, body mass index, blood pressure, fasting serum insulin levels, and insulin resistance index (fasting glucose x fasting insulin/405) were determined. The polymorphism of the beta(3)-AR gene was assessed by polymerase chain reaction-restriction fragment length polymorphism using buccal samples. Low-density lipoprotein particle size and sdLDL were measured with the electrophoretic separation of lipoproteins on the LipoPrint System (Quantimetrix, Redondo Beach, CA). The frequency of the beta(3)-AR allele was 0.19. In Arg carriers (Trp/Arg or Arg/Arg), the mean value of LDL particle size was smaller than that of non-Arg carriers (Trp/Trp) (P < .05). The area percentage of sdLDL was higher in Arg carriers (P < .05) than in non-Arg carriers. A multiple regression analysis showed that the area percentage of sdLDL was correlated with the polymorphism of the beta(3)-AR gene (P < .05), independently of age, sex, body mass index, smoking, and insulin resistance index. The present findings suggest that the beta(3)-AR gene polymorphism plays a role in the genetic predisposition to increased sdLDL, independently of insulin resistance.     

2 型糖尿病与正常人群中肾上腺素能受体基因Trp 6 4Arg多态性表型特征

目的　研究中国人群 β3 肾上腺素能受体基因 Trp64 Arg错义突变频率 ,并了解该突变对 2型糖尿病临床特征的影响。方法　应用 PCR RFLP技术检测了相互间无一级亲属关系的 12 4例 2型糖尿病患者及 13 8例非糖尿病对照人群中 β3 肾上腺素能受体基因 Trp64 Arg错义突变 ;同时检查体重指数、腰臀比例、血压 ,测定血脂及 OGTT或馒头餐试验中 0分钟及 12 0分钟血糖及胰岛素。结果　非糖尿病人群中 Trp64 Arg等位基因频率为 0 17;突变频率在糖尿病与非糖尿病之间相比无显著性差异 (P >0 0 5 ) ;突变与否间上述临床特征相比无显著性差异 (P >0 0 5 )。结论　该突变至少在其杂合子型可能不是中国人散发 2型糖尿病的主要决定因素 ;纯合子突变型可能导致 2型糖尿病早发 ,有待今后积累资料深入研究。     

β3-肾上腺素能受体基因多态性与超重和肥胖人群血管内皮功能障碍的相关研究

目的 研究β3-肾上腺素能受体（β3-AR）基因多态性对超重和肥胖人群血管内皮功能的影响以及与某些代谢指标的关系。方法 超重组234例。肥胖组152例和正常体重组175例。测定β3-AR基因Trp64Arg的基因频率，并通过高分辨率超声评价血管内皮功能。同时。测定体重指数，腰围，腰臀比，血压，知脂，空腹血糖和胰岛素，餐后血糖和胰岛素及IR指数（HOMA-IR）。结果 （1）超重，肥胖和正常体重组之间Arg64等位基因频率差异无显著性；超重组和肥胖组内皮依赖性舒张功能较无突变者显著降低。（2）无论有无基因突变。超重或肥胖组血压，甘油三酯，空腹血糖和胰岛素，餐后血糖和胰岛素及HOMA-IR等代谢指标均高于正常体重组，各组突变与无突变者之间差异无显著性。（3）血管内皮功能在无突变者与体重指数，腰围腰臀比甘油三酯，空腹血糖和胰岛素，餐后胰岛素及HOMA-IR显著负相关。在突变者与体重指数，腰围，腰臀比。空腹胰岛素和HOMA-IR显著负相关。结论 β3-AR基因多态性与超重和肥胖人群血管内皮功能障碍有关。而IR及某些代谢指标也是内皮功能障碍发生的重要因素。     

No effect of the Trp64Arg variant of the beta3-adrenergic receptor gene on weight loss by diet and exercise intervention among Japanese adults

Controversy remains as to whether the presence of the tryptophan-to-arginine (Trp64Arg) variant of the β₃-adrenergic receptor gene impedes the magnitude of body weight loss by diet and exercise intervention. The objectives of the present study were to compare the changes in body weight between carriers and noncarriers of the Trp64Arg variant before and after 6 months of diet and exercise interventions for weight loss. A total of 37 middle-aged Japanese individuals (12 carriers and 25 noncarriers of the Trp64Arg variant) participated in the study. There were no significant differences in body weight between the 2 groups at the baseline. There were significant reductions in body weight both in carriers and noncarriers, but no significant differences between the 2 groups with respect to changes in these variables. The weight changes were −2.52 kg (95% confidence interval [CI], −3.56 to −1.48) among carriers and −1.89 kg (95% CI, −2.65 to −1.13) among noncarriers, and the change in the variant carrier group minus the change in the variant noncarrier group was −0.47 (95% CI, −1.97 to 1.02). These results suggest that the presence of the Trp64Arg variant of the β₃-adrenergic receptor gene may not play a major role as a hindrance to weight reduction.     

中国人群β3肾上腺素能受体基因Trp64Arg突变与冠心病关系的研究

目的　研究中国人群 β3肾上腺素能受体 (β3AR)基因Trp64Arg突变频率以及该突变对冠心病患者临床特征的影响。方法　应用PCR/RFLP技术检测 2 52例中国人 (健康体检者 1 2 0例 ,冠心病患者 1 32例 )的 β3AR基因Trp64Arg突变基因型 ,并比较两组的临床特征。结果　 (1 )冠心病组与对照组 β3AR基因Trp64Arg突变频率分别为 1 5 9%与 1 6 7% ,两者差异无显著性 (P >0 0 5)。β3AR基因Trp64Arg突变者的体重指数显著高于正常基因型 (P <0 0 5)。 (2 )突变与否间的临床特征差异无显著性 (P >0 0 5)。结论　β3AR基因突变杂合子型 (Trp/Arg)可能不是冠心病发生的决定因素。但Trp/Arg杂合子与Trp/Trp纯合子人群间体重指数差异有显著性 ,该基因变异被证实可能与肥胖等表现存在相关