ADRB3 Trp64Arg Polymorphism Research Articles

Effect of β3-adrenergic receptor gene polymorphism andlifestyle on overweight Japanese rural residents: Across-sectional study.

ObjectivesThe β3‐adrenergic receptor (ADRB3) gene polymorphism has been implicated in obesity. Therefore, the contribution of ADRB3 Trp64Arg polymorphism to obesity‐related indicators was investigated, taking into account the lifestyle‐related factors in a Japanese rural population.MethodsA total of 600 Japanese adults aged ≥40 years in a population‐based cohort study were analyzed. The ADRB3 polymorphism was determined using peripheral blood samples. Associations between genotype and body mass index (BMI), waist circumference (WC), and body fat (BF) percentage were examined, adjusting for lifestyle‐related factors, including daily nutrient intake.ResultsThe frequency of Arg64 allele carriers was 36%. There was no significant difference in BMI, WC, or BF between the groups with or without the Trp64Arg polymorphism. Multivariable logistic regression analysis showed that the Trp64Arg polymorphism was not associated with these three indicators, but lifestyle factors including physical inactivity, higher energy and sodium consumption, and less animal protein intake were significantly related to increased WC and BF percentages.ConclusionsThe Trp64Arg polymorphism of ADRB3 gene did not contribute to increased BMI, WC, or BF. However, lifestyle‐related factors impacted these indicators in middle‐aged and older Japanese individuals living in rural areas.

Relationships among the β3-adrenargic receptor gene Trp64Arg polymorphism, hypertension, and insulin resistance in a Japanese population.

A polymorphism in the ADRB3 gene (Trp64Arg) has been associated with obesity, insulin resistance, and hypertension. This cross-sectional study investigated the relationships among this polymorphism, hypertension, and insulin resistance values (HOMA-IR) in 719 Japanese subjects aged 40 years and older. The genotype frequencies of Trp64Trp (homozygous, wild), Trp64Arg (heterozygous, variant), and Arg64Arg (homozygous, variant) were 466 (65%), 233 (32%), and 20 (3%), respectively. Insulin resistance was associated with an increased risk of hypertension in a Japanese population. This relationship was dependent on the presence or absence of the Trp64Arg polymorphism (odds ratio, 2.054; confidence interval, 1.191 to 3.541; P value, 0.010). Therefore, the Trp64Arg polymorphism of ADRB3 was associated with hypertension and insulin resistance in a healthy Japanese population. This relationship, which was dependent on the polymorphism, may predict the development of hypertension and diabetes.

Association between the Trp64Arg polymorphism of the ADRB3 gene and overactive bladder.

The β3 -adrenergic receptor (ADRB3) is very important in the regulation of the human detrusor muscle function. The well-known tryptophan64arginine polymorphism of the ADRB3 gene alters the response of the receptor to various stimuli, including adrenalin and noradrenalin, and may increase the susceptibility to develop overactive bladder (OAB). Therefore, this study was performed to determine whether ADRB3 Trp64Arg polymorphism is associated with the pathophysiology of OAB syndrome. The study group (n = 150) consists of 72 patients with OAB and 78 controls without OAB. Venous blood samples were taken from all participants to analyze the ADRB3 gene Trp64Arg polymorphism using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay. We compared the distribution of Trp64Arg polymorphism and symptom severity in both OAB and non-OAB subjects using χ2 test and Mann-Whitney's U test, respectively. The frequency of the 64Arg variant (heterozygous plus homozygous) in OAB and non-OAB subjects was 15.3% and 14.1%, respectively. There was no statistically significant difference between the OAB and non-OAB groups in regard to the distribution frequency of ADRB3 Trp64Arg polymorphism. The total frequency (OAB + non-OAB, 76 women and 74 men) of the Arg64 variant allele was 5.9% and 10.8% in women and in men, respectively. Although the frequency of the Arg64 variant was nearly twofold higher in men compared to women, the difference was not statistically significant. These results demonstrated that the ADRB3 Trp64Arg polymorphism is not significantly associated with OAB syndrome in a sample of Turkish OAB patients.

The Trp64Arg polymorphism in \u03b23 adrenergic receptor (ADRB3) gene is associated with adipokines and plasma lipids: a systematic review, meta-analysis, and meta-regression

BackgroundRecently, some studies claim that adipokines may modulate plasma lipids. More interestingly, the ADRB3 Trp64Arg polymorphism may regulate adipokines and play an essential role in lipids metabolism. This study aims to clarify the associations of ADRB3 Trp64Arg polymorphism with plasma adipokines and lipid levels.MethodsTwenty-two studies (5527 subjects) and 121 studies (54,059 subjects) were respectively identified for the association analyses of adipokines and lipids. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to estimate the strength of the Trp64Arg variant in adipokines and plasma lipids. All results were recalculated after eliminating the studies with heterogeneity.ResultsThe carriers of the C allele (Arg at 64th position was encoded by the C allele) had higher levels of leptin and lower levels of adiponectin than the non-carriers. The carriers of the C allele had higher levels of triglycerides (TG), total cholesterol (TC), and lower levels of high-density lipoprotein cholesterol (HDL-C) than the non-carriers. Subgroup analysis certified an ethnicity (Asians), disease status (obesity), and gender (females) specific association. Sensitivity analysis indicated that the analysis results were robust and stable. Meta-regression indicated that obesity was related to adiponectin.ConclusionsThe C allele carriers of Trp64Arg polymorphism had a slight but significant influence on lipid levels, and the remarkable effects specific existed in obese Asian women. The associations of Trp64Arg polymorphism with dyslipidemia may partly be mediated by the effect of this polymorphism on adipokines. The association of Trp64Arg polymorphism with obesity may partly be mediated by the effect of this polymorphism on adipokines. The C allele carriers had abnormal levels of adipokines and lipids, and it indicated that the Trp64Arg polymorphism might represent a genetic risk factor for coronary artery disease (CAD).

Stratified meta-analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was associated with coronary artery disease in Asians, but not in Caucasians.

Background:Previous studies demonstrated that ADRB3, beta-3 adrenergic receptor, participated in lipolysis and thermogenesis in adipose tissue. Consequently, this gene has attracted an increasing number of genetic studies examining its association with coronary artery disease (CAD) in different ethnicities in recent years, but no conclusion has been reached so far. The aim of this study was to explore whether the well-studied locus ADRB3 Trp64Arg in this gene confers a race-specific effect to CAD by conducting a stratified meta-analysis involving 15 independent studies and 11,802 subjects.Methods:Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. Publication bias was quantified and examined with Begg's funnel plot test and Egger's linear regression method. The overall meta-analysis or stratified meta-analysis by ethnicity was performed by using STATA 12.0 software.Results:A total of 15 eligible studies involving 5779 CAD cases and 6023 health controls were included in this meta-analysis. The pooled results indicated that ADRB3 Trp64Arg polymorphism was significantly associated with an increased risk of CAD. Further stratified analysis by ethnicity revealed that ADRB3 Trp64Arg polymorphism was significantly associated with CAD in Asians (allelic: OR = 1.48, 95%CI 1.13–1.94, P = .005; homozygous: OR = 2.66, 95%CI 1.87–3.77, P < .001; recessive: OR = 2.46, 95%CI 1.74–3.47, P < .001), but not in Caucasians (allelic: OR = 1.09, 95%CI 0.93–1.27, P = .290; homozygous: OR = 1.31, 95%CI 0.61–2.86, P = .490; recessive: OR = 1.31, 95%CI 0.60–2.84, P = 2.494).Conclusions:This meta-analysis suggests that ADRB3 Trp64Arg polymorphism confers a race-specific effect to CAD.

Meta-analysis of the association between the Trp64Arg polymorphism of the beta-3 adrenergic receptor and susceptibility to gestational diabetes mellitus

The study aimed to explore the associations between Trp64Arg polymorphism of Beta-3 Adrenergic receptor (ADRB3) and susceptibility to gestational diabetes mellitus (GDM). Relevant studies till December 2013 were identified through searching electronic databases. A meta-analysis was conducted on associations between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM. We found no association between Trp64Arg polymorphism in ADRB3 and susceptibility to GDM in overall population (Arg vs. Trp: OR = 1.20, 95%CI = 0.99–1.47, p = .16; Trp/Arg + Arg/Arg vs. Trp/Trp: OR = 1.22, 95%CI = 0.99–1.50, p = .11). In subgroup analysis on European Caucasian population, Trp64Arg in ADRB3 was associated with susceptibility to GDM. Trp64Arg polymorphism in ADRB3 had certain association with susceptibility to GDM in the European Caucasian population. Impact statement What is already known on this subject: Gestational diabetes mellitus (GDM) is recognised as carbohydrate intolerance of varied severity that begins or is first recognised during pregnancy. A missense mutation in the codon 64 of the Beta-3 adrenergic receptor (ADRB3), Trp64Arg, leads to the substitution of tryptophan by arginine in the first intracellular loop of the ADRB3 receptor. Trp64Arg Polymorphism has also been reportedly associated with increased body weight, type 2 diabetes mellitus, insulin resistance and obesity. However, other investigators have found that the Trp64Arg polymorphism of ADRB3 has no effect on insulin resistance, obesity or type 2 diabetes mellitus. What the results of the study add: Our present meta-analysis demonstrated that Trp64Arg polymorphism in ADRB3 was associated with susceptibility to GDM in the European Caucasian population. Trp64Arg polymorphism in ADRB3 may be able to predict the occurrence of GDM and used for the diagnosis of it in clinic. What the implications are of these findings for clinical practice and future research: The findings in this study may provide a basis for the further study on Trp64Arg polymorphism in future research.

The association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with myocardial infarction risk in Han Chinese

Adrenergic receptors play a key role in activating the sympathetic nervous system, which often accompanies with the development of myocardial infarction (MI). Here, we aimed to test the association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with MI risk. Genotypes were available for 717 MI patients and 612 controls. There were no detectable deviations from the Hardy-Weinberg equilibrium for all study polymorphisms. Allele frequencies differed remarkably for ADRA2B D/I (P<0.001), ADRB1 Ser49Gly (P=0.002), ADRB2 Gln27Glu (P=0.005), and ADRB3 Trp64Arg (P<0.001) polymorphisms, even after the Bonferroni correction. Systolic blood pressure was significantly lower in ADRA2B II genotype carriers than in the DD genotype carriers (P=0.006), while plasma high-density lipoprotein cholesterol was significantly higher in patients carrying ADRA2B I allele and ADRB1 49Ser allele than in patients with the DD genotype and 49Gly/49Gly genotype, respectively (P=0.018 and 0.033). Overall best interaction model consisted of ADRA2B D/I, ADRB1 Ser49Gly, dyslipidemia and hypertension, with the highest testing accuracy of 0.627 and the maximal 10-fold cross-validation consistency (P=0.017). Finally, a nomogram was depicted based on four significant polymorphisms and metabolic risk factors, and it had a better predictive utility and was internally validated with a discrimination C-index of 0.723 (P<0.001). Altogether, we identified two polymorphisms, ADRA2B D/I and ADRB1 Ser49Arg, which not only altered genetic susceptibility to MI, but also impacted on blood pressure and plasma lipid changes, and their combination with metabolic risk factors constituted the overall best interaction model.

Genetic Background, Adipocytokines, and Metabolic Disorders in Postmenopausal Overweight and Obese Women.

The relationship between the genetic background, adipocytokines, and metabolic state in postmenopausal women has not yet been fully described. The aim of this study was to determine the relationship between PPAR gamma-2 (Pro12Ala, C1431T) and ADRB3 (Trp64Arg) polymorphisms and serum adipocytokines (adiponectin, visfatin, and resistin) and metabolic disorders in 176 postmenopausal women with increased body mass (BMI ≥ 25 kg m−2). The distributions of selected alleles and genotype frequencies were determined with the PCR–RFLP method. The bioimpedance method was used to determine nutritional status, and enzyme-linked immunosorbent assays were applied to determine serum concentrations of adipocytokines. Viscerally obese postmenopausal women had higher body mass, body fat content, serum glucose, insulin, total cholesterol, LDL, triglycerides, uric acid, and HOMA-IR and a higher prevalence of the Ala12 allele. In models based on cytokine concentration, higher body mass and glucose concentration (visfatin model, p = 0.008) and higher insulin and triglyceride levels (resistin model, p = 0.002) were observed in visceral fat deposition and this was potentiated by the presence of the T1431 allele. In resistin models, co-existence of Ala12/X polymorphisms with the T1431 allele was associated with higher resistin and triglyceride concentrations (p = 0.045). In postmenopausal women, metabolic parameters are mainly determined by the distribution of body fat, but Ala12/X polymorphism may increase the metabolic disorders and this effect can be enhanced by the T1431 allele.

Genetic polymorphisms in alpha-actinin 3 and ­adrenoceptor beta genes in Austrian elite athletes and healthy controls

Background: During the last years many studies were conducted to investigate the contribution of various genetic variants to endurance and sprint/power performance of elite athletes. Data on team sport athletes are missing to a large extent. Therefore, the aim of the study was to investigate the frequency of selected polymorphisms on elite athlete status in Austrian team sport (handball, soccer), endurance and power athletes as well as in healthy control subjects. Methods: Genotype and allele frequencies of ACTN3 R577X (rs1815739), ADRB1 Ser49Gly (rs1801252), ADRB2 Arg16Gly (rs1042713), ADRB2 Gln27Glu (rs1042714) and the ADRB3 Trp64Arg (rs4994) polymorphisms were determined in 56 Austrian sprint/power athletes, 86 endurance athletes, 143 team sport athletes and 216 healthy non-athletic controls. Genomic DNA was extracted from saliva and genotyping was performed by real time polymerase chain reaction using a standard protocol. Results: Handball and soccer players had a higher frequency of the ACTN3 RR genotype and a lower frequency of RX + XX genotypes than the control group. Furthermore, the frequency of athletes being homozygous for the ADRB1 Ser49Ser genotype was significantly higher in team sport athletes in comparison to those competing in power/sprint sports. We did not detect any other differences in genotype distributions between the study groups. Conclusion: This study provides some evidence that the ACTN3 R577X and the ADRB1 Ser49Gly polymorphisms are associated with team sport performance. Larger prospective studies focusing on the genetic influence of performance development are required for confirmation of these findings.

Association between Β3-Adrenergic receptor (ADRB3) gene polymorphism with body mass index and bone mineral density in Turkish postmenopausal women

Abstract: Previous studies have suggested that β3-adrenergic receptor (ADRB3) gene is associated with body mass index (BMI), which is an important predictor of bone mineral density (BMD). However, little is known concerning the effect of the ADRB3 gene on BMD. The present study investigated the relationship between ADRB3 Trp64Arg polymorphism, BMI and BMD in Turkish postmenopausal women. 133 postmenopausal women (81 osteoporotic and 52 healthy control) were recruited. For the detection of ADRB3 Trp64Arg polymorphism, polymerase chain reaction-restriction fragment lenght polymorphism (PCR-RFLP) techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distribution of ADRB3 Trp64Arg genotypes was similar in the study groups (p>0.05). “Arg/Arg” genotype was not observed. In the osteoporotic group, subjects with “Trp/Trp” genotype tended to have lower BMI values compared to those with “Trp/Arg” genotype, the difference was closely tied to statistical significance (p=0.052). Subjects with “Trp/Trp” genotype had also lower BMD values of femoral neck (p=0.044) and total hip (p=0.043) than those with “Trp/Arg” genotype. No significant effects of the ADRB3 Trp64Arg genotypes on BMI and BMD values were found in the control group. Our results suggested that ADRB3 Trp64Arg “Trp/Trp” genotype might be associated with osteoporosis risk by affecting body mass index and bone mineral density values in Turkish postmenopausal women. Key words: β3-adrenergic receptor, gene polymorphism, body mass index, bone mineral density, postmenopausal women

Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism

β3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18-75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease. Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake (V̇O(2peak)) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of V̇O(2peak) for sex and decade. Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and V̇O(2peak) were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects. Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.

The Presence of At Least Three Alleles of theADRB3Trp64Arg (C/T) andUCP1−3826A/G Polymorphisms Is Associated with Protection to Overweight/Obesity and with Higher High-Density Lipoprotein Cholesterol Levels in Caucasian-Brazilian Patients with Type 2 Diabetes

We investigated whether the -3826A/G polymorphism (rs1800592) of the uncoupling protein 1 gene (UCP1) and the Trp64Arg polymorphism (rs4994) of the β3-adrenergic receptor gene (ADRB3) are associated with type 2 diabetes mellitus (T2DM) and features of metabolic syndrome in a Brazilian-Caucasian population. Both polymorphisms were genotyped in 1015 T2DM patients and 561 nondiabetic subjects. The combined effect of both polymorphisms on T2DM and metabolic syndrome-related parameters was analyzed according to a triallelic inheritance pattern, by which at least three minor alleles from two loci are necessary for trait manifestation. UCP1 -3826A/G and ADRB3 Trp64Arg polymorphisms were not associated with T2DM (P>0.05). Patients carrying the ADRB3 64Arg allele had higher fasting plasma glucose and high-density lipoprotein cholesterol (HDL-C) than patients with the Trp64Trp genotype (P=0.0001 and P=0.015, respectively). The 64Arg allele was also associated with protection against overweight/obesity (body mass index ≥ 25 kg/m(2); odds ratio [OR]=0.598; P=0.014). Interestingly, prevalence of overweight/obesity was lower among carriers of at least three minor alleles of the -3826A/G and ADRB3 Trp64Arg polymorphisms than among patients with fewer than three minor alleles (54.5% vs. 79.1%; OR=0.288; P=0.007, respectively). Subjects with at least three minor alleles also had higher HDL-C levels (P=0.018). UCP1 -3826A/G and ADRB3 Trp64Arg polymorphisms may have a combined effect in the modulation of overweight/obesity and HDL-C levels in type 2 diabetes mellitus (T2DM) Caucasian-Brazilian patients.

Cardiorespiratory fitness affects polymorphism in ADRB3 Trp64Arg‐caused increase in common carotid intima‐media thickness

PURPOSEIn the present study, a cross‐sectional investigation of 769 Japanese men and women (18–75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between risk of cardiovascular disease and beta3‐adrenergic receptor (ADRB3) Trp64Arg gene polymorphism.METHODSCommon carotid intima‐media thickness (ccIMT) was assessed as a risk of atherosclerosis. We measured peak oxygen uptake (VO2peak) during incremental cycle ergometer exercise test, and then the subjects were divided into high‐(High‐Fit) and low‐cardiorespiratory fitness (Low‐Fit) groups based on the median value of VO2peak in each sex and decade.RESULTSBody fat, triglyceride and plasma glucose levels were lower and HDL cholesterol levels and VO2peak were higher in High‐Fit subjects compared with in Low‐Fit subjects, but there were no significant effect of ADRB3 polymorphism. There was no significant effect of ADRB3 Trp64Arg polymorphism on ccIMT. In Low‐Fit subjects, ccIMT increased in ArgArg genotype individuals compared with TrpTrp and TrpArg genotype of ADRB3, however, had no effect on ADRB3 polymorphisms in High‐Fit subjects.CONCLUSIONThese results suggest that the higher cardiorespiratory fitness may attenuate a risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.This work was supported by a Grant‐in‐Aid for Scientific Research of Japan (#20300231, #20700563).

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

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. 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. No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027). 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 may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.

Association of beta3-adrenergic receptor (ADRB3) Trp64Arg gene polymorphism with obesity and metabolic syndrome in the Balinese: a pilot study

BackgroundPrevalence of obesity is increasing all over the world. ADRB3 Trp64Arg gene polymorphism was proposed to be associated with obesity, although inconsistent findings and differences of the Arg64 allele frequency among various ethnics were reported. Westernization was reported to increase the prevalence of obesity in developing world. In this study we determined the prevalence of obesity and metabolic syndrome among urban and rural Balinese, and studied the association of ADRB3 Trp64Arg polymorphism with obesity and MetS.FindingsA total of 528 Balinese (urban 282, rural 246) were recruited. Body mass index (BMI) and waist circumference (WC) were determined; high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic and diastolic blood pressure (SBP and DBP), and fasting plasma glucose (FPG) were measured using standard procedures. BMI and WC classifications were based on WHO classifications for Asian. Metabolic syndrome (MetS) was defined as described in the Joint Interim Statement. Chi-square test was employed to test the association between the ADRB3 Trp64Arg genotype and disease traits.Urban have higher BMI (p = 2.8 × 10-13), WC ( p < 2.2 × 10-16), TG (p = 0.0028), DBP (p = 1.8 × 10-5), and lower HDL-C (p = 0.0376) when compared to rural. Abdominal obesity and MetS prevalence were significantly higher in urban as compared to rural (both p < 0.001). The Arg64 allele frequency was similar between urban (0.06) and rural (0.05). The Arg64 rural female carriers have higher BMI and WC as compared to their Trp64 counterparts (p = 0.041 for BMI and p = 0.012 for WC), and consequently higher abdominal obesity prevalence (p = 0.007). Comparison between male and female, as well as urban and rural, showed different prevalence of MetS co-morbidities. Abdominal obesity and hypertriglyceridaemia were consistently appeared in all groups, suggesting to play a role as determinant of MetS in both urban and rural.ConclusionsPrevalence of obesity and MetS in urban were two times higher when compared to rural. Abdominal obesity and hypertriglyceridaemia appears to be the key determinant of MetS in both urban and rural Balinese. Our results indicated an association of the ADRB3 Trp64Arg gene polymorphism with obesity in the rural female.

Influence of beta 3-adrenergic receptor Trp64Arg polymorphism on the improvement of metabolic syndrome by exercise-based intervention in Japanese middle-aged males

To date, there have been few intervention studies concerning the association of metabolic syndrome with beta 3-adrenergic receptor (ADRB3) Trp64Arg polymorphism, although ADRB3 Trp64Arg polymorphism has been reported to be associated with weight gain and insulin resistance by several intervention programs. We examined the influence of ADRB3 Trp64Arg polymorphism on the improvement of metabolic syndrome by an exercise-based intervention program. Thirty-six male employees who satisfied the metabolic syndrome criteria participated in a three-month exercise-based intervention program (average age, 49 ± 6 years old). The improvement rate of metabolic syndrome after the intervention was compared between subjects with and without ADRB3 Trp64Arg polymorphism. The Mantel-Haenszel test was employed to adjust the age, diet, and exercise in analysis of the influence of ADRB3 Trp64Arg polymorphism on metabolic syndrome. The Trp64Arg genotype of the β3-adrenoceptor gene was examined in peripheral blood leukocyte DNA by TaqMan PCR assay. The distribution of polymorphism was 23 (Trp/Trp), 13 (Trp/Arg), and 0 (Arg/Arg). The metabolic syndrome improvement rates after intervention were 21.7% (Trp/Trp) and 53.8% (Trp/Arg) (p = 0.050). After adjustment individually for age, calorie limitation, and 10,000 or more and 12,000 or more steps of walking per day during intervention, the odds ratios of the Trp/Arg genotype for improvement of metabolic syndrome relative to that of the Trp/Trp genotype were 5.1 (p = 0.043), 4.9 (p = 0.051), 3.7 (p = 0.074), and 5.0 (p = 0.045), respectively. The results suggested that ADRB3 Trp64Arg polymorphism influences the metabolic syndrome improvement rate by exercise-based intervention program.

Trp64Arg Polymorphism of the ADRB3 Gene Predicts Hyperuricemia Risk in a Population from Southern Spain

To study the role of Trp64Arg polymorphism of the ADRB3 gene in the risk of developing hyperuricemia in 1051 subjects from southern Spain, with a followup of 6 years. The inclusion of plasma levels of uric acid as a diagnostic criterion to define the metabolic syndrome is under discussion. Genes responsible for insulin resistance could contribute to the development of hyperuricemia. Previous cross-sectional studies have suggested ADRB3 as a possible candidate gene in the development of hyperuricemia and insulin resistance. A prospective, population-based, cohort study of 1051 persons examined in 1997-98 and reassessed at a second examination 6 years later. The metabolic phenotype was assessed at baseline and again at the followup. Insulin resistance was measured by homeostasis model assessment. The Trp64Arg polymorphism of ADRB3 was detected by real-time polymerase chain reaction. Subjects were considered normouricemic if their serum uric acid levels were <or=7 mg/dl for men or <or= 6 mg/dl for women. Carriers of the Arg64 allele who were normouricemic at baseline had a higher risk of developing hyperuricemia 6 years later (p = 0.017, OR 2.3, 95% CI 1.1-4.6). Multivariate logistic regression analysis showed that the OR of having hyperuricemia at the 6-year followup was significantly associated with the Arg64 allele, after adjusting for age, weight gain, baseline levels of triglycerides, serum uric acid, and insulin resistance (OR 3.1, 95% CI 1.3-7.1). Trp64Arg polymorphism of the ADRB3 gene predicted the risk of developing hyperuricemia in this adult population.

Effects of UCP2 –866 G/A and ADRB3 Trp64Arg on rosiglitazone response in Chinese patients with Type 2 diabetes

The aim of this study was to explore the impact of UCP2 and ADRB3 genetic polymorphisms on the therapeutic efficacy of rosiglitazone in Chinese Type 2 diabetes (T2DM) patients. A total of 199 T2DM patients and 155 healthy volunteers were enrolled to identify UCP2 -866 G/A genotypes, and 273 T2DM patients and 166 controls were genotyped for Trp64Arg of ADRB3 by polymerase chain reaction-restriction fragment length polymorphism assay. Nine patients with GG genotype and 27 with GA+AA genotype of UCP2 -866 G/A, 11 with Trp64Trp genotype and 25 with Trp64Arg genotype of ADRB3 received oral rosiglitazone as a single-agent therapy (4 mg day(-1)) for 12 weeks. Serum fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin (HbA(1c)), fasting serum insulin, postprandial serum insulin (PINS), triglycerol (TG), cholesterol, homeostasis model assessment for insulin resistance, leptin and adiponectin in all T2DM patients were determined before and after rosiglitazone treatment. There were no differences in allele frequency of either ADRB3 Trp64Arg or UCP2 -866 G/A between T2DM patients and control subjects. The A allele carriers of UCP2 in the T2DM patients had significantly lower PINS (61.5 +/- 34.3 vs. 41.6 +/- 28.7 mU l(-1), P < 0.01) (37.57, 59.16 vs. 34.82, 49.39) and low-density lipoprotein (LDL)-cholesterol compared with GG genotypes (3.4 +/- 1.1 vs. 2.7 +/- 1.1 mmol l(-1), P < 0.05) (2.64, 3.52 vs. 2.66, 3.15). After rosiglitazone treatment for 12 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller attenuated PINS (-3.82 +/- 13.2 vs.-42.1 +/- 30.7 mU l(-1), P < 0.01) (9.45, 51.31 vs. 0.48, 11.88) and greater attenuated HbA(1c) (-1.85 +/- 1.62 vs.-0.61 +/- 0.80, P < 0.05) (0.14, 1.37 vs. 1.10, 2.38) compared with GG genotypes, and ADRB3 Trp64Arg had greater attenuated serum TG (-3.88 +/- 2.77 vs.-0.24 +/- 1.16 mmol l(-1), P < 0.05) (-0.19, 2.74 vs. 1.19, 1.45) and smaller attenuated LDL-cholesterol (1.08 +/- 1.36 vs.-0.36 +/- 0.99, P < 0.01) (-1.26, 0.78 vs.-1.26, 0.79) as well as reduced enhanced adiponectin (1.57 +/- 1.10 vs. 3.15 +/- 2.12 mmol l(-1), P < 0.05) (1.68, 4.08 vs.-9.18, 11.40) compared with ADRB3 Trp64Trp. UCP2 -866 G/A and ADRB3 Trp64Arg polymorphisms are associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients.

Arg64Variant of the ß3-Adrenergic Receptor is Associated With Gallstone Formation

The beta3-adrenergic receptor (ADRB3) is a transmembrane receptor highly expressed in adipose tissue and thought to be involved in the regulation of lipolysis. ADRB3 is also highly expressed in gallbladder tissue where it may be involved in gallbladder contraction. Because polymorphisms of ADRB3 are present in populations with a high prevalence of gallstones (e.g., Pima-Indians, obese subjects), we hypothesized that known polymorphisms for ADRB3 (Trp64Arg) may represent an independent risk factor for gallstone disease. The EMIL cross-sectional study investigated the health behavior and prevalence of chronic diseases in a small Southwestern German town of 12,475 inhabitants. From 3,893 randomly selected citizens 2,147 subjects were enrolled and screened for gallstones employing ultrasonography. Blood samples were drawn for biochemical analysis and isolation of genomic DNA. ADBR3 genotypes were determined by TaqMan SNP Assay. We identified 171 (8%) gallstone carriers of whom 143 participated (46 male, 97 female), with a mean age of 51.4, and mean BMI of 29.3 kg/m2. For these subjects an age, gender and BMI matched partner without gallstones was recruited from the study population. Genotyping for ADRB3 revealed an Arg64 allele frequency of 5.9 versus 0.7% (HR = 11.9, P < 0.05) compared with controls. Our results indicate that the ADRB3 Trp64Arg polymorphism is associated with gallstone disease thereby representing a genetic marker that identifies subjects at higher risk for gallstone formation.

Post-exercise oxidative stress and obesity in postmenopausal women: The role of beta 3-adrenergic receptor polymorphism

Aim. Some studies indicate that the Trp64Arg polymorphism in the gene encoding the β3-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the present study was to evaluate the frequency of this polymorphism and its relationship with obesity and oxidative stress in postmenopausal women. Material and methods. We performed the study on 200 women, aged 50–60 years. Estimation of anthropometric parameters and total body fat, android and gynoid fat deposits was carried out using dual-energy X-ray absorptiometry. Oxidative stress was estimated by measurement of thiobarbituric acid-reactive substances (TBARS) in serum. Blood for analysis was collected before, directly after and 6 h after a 30-min physical test on a cycle ergometer. ADRB3 genotyping was performed by polymerase chain reaction. Results. The frequency of Trp 64 /Arg 64 genotype in the investigated population was 12%, and of Trp 64 /Trp 64 was 87%. The Arg 64 /Arg 64 genotype was present in only 1% of women. Women bearing the Trp 64 /Arg 64 genotype did not differ in any measured anthropometric parameters from women bearing the Trp 64 /Trp 64 genotype. Moreover, genotype had no influence on oxidative stress parameters. Likewise, in both groups, mean plasma level of TBARS was increased significantly (p < 0.05) directly after the endurance test and remained elevated 6 h after the test. Conclusions. The Trp64Arg polymorphism of ADRB3 seems to not be related to obesity in postmenopausal women. Moreover, the Trp64Arg polymorphism has no influence on oxidative stress intensification after standardized physical effort in postmenopausal women.