β_3-肾上腺素能受体基因与2型糖尿病关系的研究

目的　探讨 β3 -肾上腺素能受体 (β3 -AR)基因Trp64Arg突变与 2型糖尿病 (NIDDM )有无关联。 方法　对130例糖尿病患者和 130例健康对照者 ,采用聚合酶链反应 -限制性酶切酶片段长度多态性技术检测 β3 -AR基因型 ,并测定BMI、WHR、血压、TC、TG、HDL -C、载脂蛋白A、载脂蛋白B和Lp(a)。结果　 (1)糖尿病病例组β3 -ARArg等位基因频率 (14 7% )略高于对照组 (14 2 % ) ,两组基因型和等位基因频率分布差异无显著性 (P >0 0 5 )。 (2 )糖尿病病例组中Trp64Arg与BMI相关。女性糖尿病人群中 ,肥胖与体重正常者Arg64等位基因频率分别为 19 8%和 5 7% ,该突变与BMI呈显著正相关 (P =0 0 10 )。结论　 2型糖尿病 (NIDDM)患者β3 -AR基因突变与BMI有关     

β3-肾上腺素能受体及UCP2基因多态性与儿童单纯性肥胖的关系

目的研究β3-肾上腺素能受体基因的Trp64Arg变异与UCP2基因Ala55Val变异对儿童单纯性肥胖的影响是否存在交互作用,为儿童单纯性肥胖的防治提供理论依据。方法用聚合酶链反应—限制性片段长度多态性方法(PCR-RFLP)检测UCP2基因Ala55Val及β3-AR基因Trp64Arg的多态性,比较病例组与对照组各基因型的发生频率以及不同基因型之间BMI、血液生化指标的差异。结果β3-AR的变异频率在单纯性肥胖组和对照组差异有统计学意义(P=0.038),UCP2基因的变异频率在2组之间差异也有统计学意义(P=0.045)。当只有单一的UCP2或β3-AR变异基因型时,病例组与对照组的频率分布差异无统计学意义;但当UCP2和β3-AR基因同时发生变异时,病例组的变异基因频率明显高于正常组(OR=4.002,95%可信区间为1.636～9.884)。结论UCP2基因Ala55Val变异与β3-AR基因Trp64Arg变异同时发生时,会明显增加儿童单纯性肥胖症发生的危险性。     

β3-肾上腺素能受体基因与肥胖关系

目的　探讨β3-肾上腺素能受体 （β3- AR）基因 Trp6 4Arg突变与肥胖的关系。方法　采用聚合酶链反应 -限制性酶切片段长度多态性技术检测β3- AR基因型 ;同时检查体质指数 （BMI）等指标 ,观察在 147例肥胖患者和 10 6例健康对照者中 ,β3- AR基因型与 Arg6 4等位基因的频率分布以及不同体质指数的人群中 ,其突变基因的分布情况。结果　肥胖组 Arg6 4等位基因的频率（2 0 .3% ）显著高于对照组 （10 .2 % ） （χ2 =10 .14,P =0 .0 0 1） ,突变基因型 Trp6 4Arg、Arg6 4Arg的分布频率 （38.7%和 0 .9% ）也高于对照组 （19.0 %和 0 .7% ）。在女性人群中 ,肥胖者 Trp6 4Arg基因型及 Arg6 4等位基因频率 （4 0 .6 %和 2 0 .3% ）显著高于非肥胖者 （16 .7%和 9.5 % ） ,且差异有显著性 （P <0 .0 1）。结论　β3-肾上腺素能受体基因 Trp6 4Arg突变可能与体脂增多有关     

学龄儿童β3-肾上腺素能受体基因变异的分布

目的 了解学龄儿童中β3-肾上腺索能受体（β3-AR)基因氧基酸序列第64位密码子上的色氨酸(Trp64Arg)变异型的分布特点及其与肥胖的关系，方法 用限制性片段基困长度多态性法对177名儿蛊进行了基因多态性检测，同时测量身高、体重。结果 变异型等位基因(C)在被调查对象中出现的频率为0．240，其中男童为0226，女童为0．267。肥胖女童中变异等位基因(C)、Trp64Arg变异基因型的出现频率明显高于正常体重者。有父母肥胖或有母亲肥胖的家庭中，女童出现Trp64Arg变异的频率分别为713．3％，71．4％。具有Trp64Arg变异儿童的体重、BM1明显较高，具有Trp64Arg变异的女童发生肥胖的危险性为4．5，结论 基因Trp64Arg变异在学龄儿童中有一定的分布，且以肥胖女童为多。     

β3-AR基因多态性与高血糖人群膳食干预效果

目的探讨β3AR基因多态性与高血糖人群膳食干预效果的关系,为糖尿病的膳食干预提供遗传学依据。方法从南京市8个社区抽取233名汉族高血糖者,随机分为复合干预组(154人)和对照组(79人)。干预组给予粗粮干预和进行健康进座,对照组不采取任何措施,试验周期6个月。结果干预组Trp/Trp基因型者体质指数(BMI)、腰臀比(WHR)、舒张压(DBP)、空腹血糖(FBG)、血总胆固醇(TC)水平明显降低,高密度脂蛋白胆固醇(HDLC)水平明显上升(P<0.05);Trp/Arg基因型组BMI、WHR、FBG水平明显降低,HDLC水平明显上升(P<0.05)。Arg/Arg基因型组无明显变化。此外,Trp/Trp型人群的BMI、WHR和FBG下降的干预效果明显大于Trp64Arg型和Arg/Arg型,而Trp64Arg型人群的这3项指标下降又明显大于Arg/Arg型(P<0.05)。结论高血糖人群膳食干预效果因β3AR基因型不同而有差异,其中,Trp/Trp人群对膳食干预效果最佳,Trp/Arg次之,而Arg/Arg效果较差。     

2型糖尿病患者β3-肾上腺素能受体基因突变与肥胖的关系

目的 研究2型糖尿病患β3－肾上腺素能受体基因突变与肥胖的关系。方法 采用聚合酶链反应－限制性内切酶片段长度多态性（PCR－RFLP）技术检测了154例2型糖尿病患β3－肾上腺素能受体基因Trp64Arg错义突变;同时检查体质指数、腰臀比值、血压及测定血脂等指标。结果 糖尿病伴有肥胖Trp64Arg基因型的频率为42．5％,Arg64等位基因的频率为22．6％;突变频率在糖尿病伴有肥胖与糖尿病体重正常之间差异有显性。突变与体质指数、收缩压、舒张压及HDL－C相比有统计学意义。结论 糖尿病患β3－肾上腺素受体基因突变与肥胖可能有关。     

β3—肾上腺素能受体基因与肥胖关系

目的 探讨β3－肾上腺素能受体（β3－AR）基因Trp64Arg突变与肥胖的关系。方法 采用聚合酶链反应－限制性酶切片段长度多态性技术检测β3－AR基因型;同时检查体质指数（BMI）等指标,观察在147例肥胖患和106例健康对照中,β3－AR基因型与Arg64等位基因的频率分布以及不同体质指数的人群中,其突变基因的分布情况。结果 肥胖组Arg64等位基因的频率（20．3％）显高于对照组（10．2％）（χ^2=10.14,P=0.001),突变基因型Trp64Arg、Arg64Arg的分布频率38．7％和0．9％）也高于对照组（19．0％和0．07％）。在女性人群中,肥胖Trp64Arg基因型及Arg64等位基因频率（40．6％和20．3％）显高于非肥胖（16．7％和9．5％）,且差异有显性（P＜0．01）。结论 β3－肾上腺素能受体基因Trp64Arg突变可能与本脂增多有关。     

β3肾上腺素能受体基因多态与新疆哈萨克族人腹型肥胖和代谢综合征的相关研究

目的 检测新疆哈萨克族人群中β3肾上腺素能受体(β3-AR)Trp64Arg位点的等位基因频率和基因型频率,分析β3-AR基因在腹型肥胖、代谢综合征发生、发展中的作用.方法 应用聚合酶链反应和限制性片断长度多态性技术检测172例代谢综合征(MS)、92例单纯腹型肥胖和92例正常人的基因型,同时测定相关的生化指标,进行病例-对照研究.结果 β3-AR Trp64Arg位点的基因型频率在三组间差异无统计学意义.结论 β3-AR Trp64Arg多态与哈萨克族人腹型肥胖、MS的发生无明显关联.     

β3-肾上腺素能受体基因变异与肥胖原发性高血压关系的七年随访研究

目的 探讨β3-肾上腺素能受体基因变异与肥胖原发性高血压的关系.方法 研究纳入单纯肥胖者(体重指数≥25 kg/m~2)377例,男226例,女151例.根据基线时测定的β3-肾上腺素能受体基因型分为Trp64纯合子和Arg64携带者,测定基线时体重指数、血压、血脂、空腹血糖和空腹胰岛素,计算胰岛素抵抗指数(HOMA-IH).7年后对此人群进行随访.结果 7年后Arg64携带者原发性高血压发生率显著高于Trp64纯合子[52.7%(69/131)比37.0%(91/246),P<0.01] ,这种差异表现在男性[59.5%(50/84)比45.1%(64/142),P<0.05] .Trp64纯合子和Arg64携带者男性原发性高血压发生率也均高于女性(P<0.01或<0.05).基线资料显示,Arg64携带者的体重指数、血压、血脂、空腹血糖、空腹胰岛素和HOMA-IR等指标与Trp64纯合子比较差异无统计学意义.7年后Trp64纯合子血压升高(9.7±4.3)/(5.4±4.0)mm Hg(1 mm Hg=0.133 kPa),Arg64携带者血压升高(12.8 ±5.2)/(7.9±4.7)mm Hg,后者三酰甘油、空腹胰岛索和HOMA-IR升高也较前者更显著(P<0.05).Logistic回归分析显示β3-肾上腺素能受体基因Trp64Arg变异、男性、中心性肥胖和胰岛素抵抗与肥胖原发性高血压发生相关.结论 β3-肾上腺素能受体基因变异是男性肥胖原发性高血压的独立危险因素.     

β3—肾上腺素能受体基因与2型糖尿病关系的研究

目的 探讨β3－肾上腺素能受体（β3－AR）基因Trp64Arg突变与2型糖尿病（NIDDM）有无关联。方法 对130例糖尿病患和130例健康对照,采用聚合酶链反应－限制性酶切酶片段长度多态性技术检测β3－AR基因型,并测定BMI、WHR、血压、TC、TG、HDL－C、载脂蛋白A、载脂蛋白B和Lp(a)。结果 （1）糖尿病病例组β3－AR Arg等位基因频率（14．7％）略高于对照组（14．2％）,两组基因型和等位基因频率分布差异无显性（P＞0．05）。（2）糖尿病病例组中Trp64Arg与BMI相关。女性糖尿病人群中,肥胖与体重正常Arg64等位基因频率分别为19．8％和5．7％,该突变与BMI呈显正相关（P＝0．010）。结论 2型糖尿病（NIDDM）患β3－AR基因突变与BMI有关。     

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 aim of this study was to determine whether there was an association between body fat distribution, blood lipid profiles, and beta 3-adrenergic receptor gene polymorphism in Korean middle-aged women. Subjects were grouped according to BMI as obese (> or = 5 BMI, n = 95) or non-obese (BMI<25, n = 93). The Trp64Arg mutation of the beta 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<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 (chi-square = 4.943, p<0.05) difference between the two groups. Frequency of the Arg64 allele in the obese group (16.84%) showed a significant (chi-square = 4.185, p<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 beta 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 beta 3-adrenergic receptor gene with prevalence of abdominal obesity or dyslipidemia in Korean middle-aged women.     

Metabolic syndrome and ADRB3 gene polymorphism in severely obese patients from South Italy

OBJECTIVE: To evaluate the prevalence of beta(3)-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity. DESIGN: Cross-sectional outpatients study. PATIENTS AND METHODS: In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method. RESULTS: Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (beta=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects. CONCLUSION: We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.     

β3-受体基因多态性对减重效果的影响

目的探讨β3-受体基因多态性对减重效果的影响。方法单纯肥胖者（体重指数≥25kg/m2）274例，测定β3-AR基因Trp64Arg的基因频率。并经过强化生化方式减重干预12个月，干预前后测定体脂、血压、血脂、空腹血糖和胰岛素，计算IR指数（HOMA—IR）。结果按照减重程度分组，理想达标组99例，一般达标组128例和未达标组47例。未达标组Arg基因频率显著高于理想达标组（x^2=4．80，P〈0．05）。减重干预前Arg64携带者组腰围、腰臀比、空腹血糖及HOMA—IR均明显高于Trp64纯合子组（均P〈0．05）。减重干预后，Trp64纯合子组体脂、血压、总胆固醇、甘油三酯、空腹胰岛素及HOMA—IR均显著降低（P〈0．05或P〈0．01），Arg64携带者组上述指标中除体重指数较前降低外（P〈0．05），其余各项指标均无显著变化。结论β3～AR基因Trp64Arg变异与强化生活方式干预后减重不易达标有关。     

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not associated with training-induced changes in body composition: The HERITAGE Family Study

OBJECTIVE: To investigate the association between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and changes in body composition in response to endurance training. RESEARCH METHODS AND PROCEDURES: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat-free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre- and post-training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. RESULTS: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training-induced changes for any of the body composition phenotypes in both men and women. DISCUSSION: These results suggest that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene is not related to changes in body composition in response to exercise training.     

Association of BMI with the Beta3 Adrenergic Receptor Gene Mutation: A Meta-Analysis

The beta3 adrenergic receptor (ADRB3) is a part of the adrenergic system, which is known to play a key role in energy metabolism. The relationship between the Trp64Arg variant of ADRB3 and body mass index (BMI) has been widely examined; however, the results of these studies have been inconsistent. Therefore, we performed a meta-analysis of the relationship between an ADRB3 variant and BMI in 2008. Our results suggested that the Trp64Arg variant of ADRB3 was associated with BMI in East Asians, but not Europeans. Additionally, our report showed the importance of meta-analyses in the field of genetic association studies for common traits. In 1995, Yoshida et al. reported that the Trp64Arg variant of ADRB3 was related to difficulty in weight loss. The decrease in body weight in obese subjects with the mutation was lower than that in obese subjects without the mutation following a 3 month combined low-calorie diet and exercise regimen. However, subsequent studies have yielded inconsistent results. Accordingly, further studies are needed to reliably assess and interpret gene-phenotype associations with this ADRB3 variant.     

Increased risk of obesity resulting from the interaction between high energy intake and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy Japanese men

BACKGROUND: Few studies have investigated the interaction between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene (ADRB3) and environmental factors. This study aimed to investigate whether energy intake affects the relationship between this polymorphism and obesity. METHODS: Healthy Japanese men (n=295; age 46.1+/-11.5 years (mean +/-standard deviation); waist circumference 83.9+/-9.3 cm; body mass index (BMI) 23.3+/-3.3 kg/m2) recruited in a Japanese chemical industry firm were eligible for analysis. Daily energy intake, protein, fat, and carbohydrate (PFC) ratio and daily physical activity were assessed by self-reported questionnaires. Genotyping for the polymorphism was performed with written informed consent. RESULTS: When the subjects were classified into two groups according to presence of the polymorphism, the groups were not significantly different in waist circumference or BMI. Quartile classification of energy intake, however, demonstrated a significantly larger ratio of obese subjects to non-obese subjects in the group with the polymorphism in the highest 4th quartile alone. Multiple logistic regression analysis also revealed that the presence of the polymorphism increased the risk of obesity significantly in the 4th quartile alone (adjusted odds ratio=3.37, 95% confidence interval=1.12-10.2). CONCLUSION: Presence of the polymorphism alone does not significantly increase the risk of obesity. However, high energy intake interacts with the polymorphism and leads to a significant increase in risk of obesity. The Trp64Arg polymorphism of ADRB3 warrants consideration, along with other polymorphisms involved in the development of obesity, for tailor-made prevention of obesity.     

Effects of beta2-adrenergic receptor gene variants on adiposity: the HERITAGE Family Study

We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenergic receptor gene were associated with body-fat and fat-distribution phenotypes measured before and in response to a 20-week endurance-training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene-by-obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the beta2-adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).     

Association of BMI with the beta3-adrenergic receptor gene polymorphism in Japanese: meta-analysis.

OBJECTIVE: To assess the effect of the Trp64Arg polymorphism in the beta3-adrenergic receptor gene (ADRB3) on body mass index (BMI) in the Japanese population. RESEARCH METHODS AND PROCEDURES: We selected studies that evaluated the association between BMI and ADRB3 polymorphism among Japanese, using MEDLINE and PubMed. After data collection, an extension of ANOVA was performed to assess the differences according to the genotype. RESULTS: In a total of 35 subgroups including 2316 subjects with the Trp64Arg variant and 4266 subjects without this variant, the weighted mean difference in BMI was 0.26 kg/m(2) (95% confidence interval: 0.18 to 0.42; p < 0.01), indicating that variant carriers exhibited higher BMI than did normal homozygous subjects. DISCUSSION: Although it is known that the allele frequency of the ADRB3 polymorphism differs among races, this study focuses on the Japanese population, which has a high allele frequency of ADRB3 polymorphism. We assumed that statistical errors would be prevented due to the sufficient number of subjects. In conclusion, the results support the hypothesis that ADRB3 gene polymorphism is associated with BMI.