ADRB3 Rs4994 Research Articles

Genetic Variants of Obesity in Malaysia: A Scoping Review.

Obesity is a pressing public health issue in Malaysia, involving not only excess weight but also complex metabolic and physiological changes. Addressing these complexities requires comprehensive strategies, including understanding the population-level differences in obesity susceptibility. This review aims to compile the genetic variants studied among Malaysians and emphasize their implications for obesity risk. Relevant articles published up to March 2024 were extracted from the Scopus, PubMed, and ScienceDirect databases. The review process was conducted in accordance with the PRISMA-ScR guidelines. From an initial pool of 579 articles, 35 of these were selected for the final review. The identified gene variants, including LEPR (K656N), LEP (G2548A-Indian only), ADIPOQ (rs17366568), UCP2 (45bp-I/D), ADRB3 (rs4994), MC3R (rs3827103), PPARγ (pro12Ala-Malay only), IL1RA (intron 2 VNTR), NFKB1 (rs28362491), and FADS1 (rs174547-Indian only), showed significant associations with obesity as measured by the respective studies. Overall, more intensive genetic research is needed, starting with population-based profiling of genetic data on obesity, including among children. Sociocultural contexts and environmental factors influence variations in genetic elements, highlighting the need for targeted interventions to mitigate the impacts of obesity in the population.

Intergenic interactions of <i>ADRB2</i>, <i>ADRB3</i>, <i>FABP2</i> and <i>PPARG</i> genes in children with asthma associated with obesity

Introduction. The constant increase in the prevalence of bronchial asthma in children and adolescents raises concerns about a parallel increase in obesity-related asthma and suggests that obesity alters asthma towards a phenotype that is more difficult to control. The development of multifactorial diseases (asthma and obesity) is based on complex intergenic interactions that must be taken into account when predicting the risk of developing an unfavorable course of the pathological process.Aim. To study the contribution of polymorphic variants of the metabolism genes rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu) of the β2-adrenoceptor gene (ADRB2), rs4994 Trp64Arg of the β3-adrenoceptor gene (ADRB3), rs1801282 of the PPARG gene, rs1799883 Ala54Thr of the FABP2 gene using Multifactor Dimensionality Reduction (MDR) in patients with asthma and obesity to identify significant intergenic interactions.Materials and methods. 161 children withasthma were examined, including 59 patients with obesity of 1-3 degrees. The examination included general clinical, laboratory, and functional methods. The level of asthma control was determined according to the GINA criteria (2018). The study of gene polymorphisms was carried out by real-time polymerase chain reaction using sets of “Metabolism” (Research and Production Company “Litekh”, Moscow) on the CFX-96 Biorat device (USA).Results. When comparing groups of children with asthma associated with obesity, a significant model of the interaction of the ADRB3 and FABP2 genes was determined. This two-locus model of intergenic interaction. According to this model, children with bronchial asthma with the following genotypes have an increased risk of obesity: Trp64Arg ADRΒ3 and Ala54Thr FABP2; Trp64Arg ADRΒ3 and Thr 54Thr FABP2; Trp64 Trp ADRΒ3 and Ala54Thr FABP2; Trp64 Trp ADRΒ3 and Thr 54Thr FABP2. In patients with AD associated with obesity and lack of disease control, we identified another statistically significant two-locus model of the interaction of the rs1042713 genes of the ADRB2 gene and PPARG. According to this model, children with the following genotypes have an increased risk of lack of disease control in patients with obesity-associated asthma: Arg16Gly ADRB2 and Pro12Ala PPARG; Arg16Gly ADRB2 and Ala12Ala PPARG; Gly16Gly ADRB2 and Pro12Ala PPARG; Gly16Gly ADRB2 and Ala12Ala PPARG.Conclusion. The obtained results of the analysis of intergenic interactions indicate that a key role in the formation of predisposition to obesity in asthma patients belongs to the association of polymorphic variants of the ADRB3 (rs4994) and FABP2 (rs1799883) genes, and the risk of uncontrolled asthma in obese children are patients with a combination of polymorphisms rs1042713 of the ADRB2 gene and rs1801282 of the PPARG gene, as evidenced by revealed two-locus models of intergenic interactions that determine the predisposition to obesity in children with asthma and affect the course of the disease. Identification of genetic predictors of both asthma and obesity is important for identifying individuals with an increased risk of developing this disease, and requires further study in the search for probable cause-and-effect relationships and the creation of personalized programs depending on polymorphic gene variants.

Effects of the Trp64Arg Polymorphism in the ADRB3 Gene on Body Composition, Cardiorespiratory Fitness, and Physical Activity in Healthy Adults.

The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, overweight individuals, and obese and diabetic patients, but it has not been studied in young and healthy adults so far. In the present study, we examined the association of ADRB3 rs4994 polymorphism with body composition, somatotype, cardiorespiratory fitness and physical activity in young, healthy adults (N = 304). All subjects had anthropometric measurements, and somatotypes were assessed using the Heath-Carter method. In addition, cardiorespiratory fitness and physical activity levels were assessed. Genotyping for the ADRB3 gene was performed using a PCR-RFLP method. In the male group, body components were associated with the Trp64Trp genotype (waist circumference (p = 0.035), hip circumference (p = 0.029), BF (%) (p = 0.008), and BF (kg) (p = 0.010), BMI (p = 0.005), WHtR (p = 0.021), and BAI (p = 0.006)). In addition, we observed that the Trp64Trp genotype was associated with somatotype components (p = 0.013). In contrast, the Arg allele was associated with the ectomorphic components (0.006). We also observed a positive impact of the Trp64Trp genotype with maximal oxygen uptake (p= 0.023) and oxygen pulse (p = 0.024). We observed a negative relationship of the Trp64Trp genotype in the female group with reported moderate-intensity exercise (p = 0.036). In conclusion, we found an association of the Trp64 allele with anthropometric traits, somatotype and parameters describing physical performance in the male group. In the female subpopulation, we only found an effect of the polymorphism Trp64Arg on the level of physical activity for moderate-intensity exercise.

The Predictive Ability of Total Genotype Score and Serum Metabolite Markers in Power-Based Sports Performance Following Different Strength Training Intensities — A Pilot Study

Muscular power is one of the factors that contribute to an athlete’s performance. This study aimed to explore the predictive ability of total genotype score (TGS) and serum metabolite markers in power-based sports performance following different strength training (ST) intensities. We recruited 15 novice male field hockey players (age = 16.27 ± .12 years old, body mass index = 22.57 ± 2.21 kg/m2) and allocated them to; high-intensity strength training (HIST, n=5), moderate intensity strength (MIST, n=5), and control group (C, n=5). Both training groups completed an eight-week ST intervention. Pre- and post-training muscular power (vertical jump) was measured. The participants were genotyped for; ACE (rs1799752), ACTN3 (rs1815739), ADRB3 (rs4994), AGT (rs699), BDKRB2 (rs1799722), PPARA (rs4253778), PPARGC1A (rs8192678), TRHR (rs7832552), and VEGF (rs1870377). TGS was calculated to annotate for strength-power (STP) and endurance (END) qualities. Subsequently, serum metabolomics analysis was conducted using Liquid chromatography-mass spectrometry Quadrupole-Time-of-Flight (LC-MS QTOF) to profile differentially expressed metabolite changes induced by training. Multiple regression analysis was conducted to explore the ability of TGS and differentially expressed metabolite markers to predict muscular power changes following the intervention. Multiple Regression revealed that only TGS STP might be a significant predictor of muscular power changes following MIST (adjusted R2=.906, p<.05). Additionally, ST also resulted in significant muscular power improvement (p<.05) and perturbation of the sphingolipid metabolism pathway (p<.05). Therefore, selected gene variants may influence muscular power. Therefore, STP TGS might be able to predict muscular power changes following MIST.

ASSOCIATION BETWEEN SPORT RELATED POLYGENIC PROFILE AND MAGNITUDE OF PHYSICAL PERFORMANCES CHANGES FOLLOWING RESISTANCE TRAINING AMONG NOVICE FIELD HOCKEY ATHLETES

Background: Studies have shown that inter-individual variation in response to resistance training is attributed to genetic variation. Aim: To correlate total genotype scores (TGS) with the magnitude of physical performances (skeletal muscle mass, muscular strength, muscular power, performance decrement, and VO2max) change, following 8 weeks of resistance training. Methods: We included forty-five (N=45) participants (age = 16.53 ± .5 years old, body mass = 61.03 ± 6.67 kg, height = 1.67±.05 m) and randomly assigned into; high intensity resistance training (n=15), moderate intensity resistance training (n=15) and a control group (n=15). They were prescribed with the same upper and lower body exercise routines. Pre- and post-test physical performances were measured. Genotyping was conducted using in-house designed allele-specific polymerase chain reaction assays. TGS for nine SNPs: Angiotensin Converting Enzyme, ACE rs1799752; Alpha-acitin-3, ACTN3 rs1815739; Adrenergic Receptor B3, ADRB3 rs4994; Angiotensinogen, AGT rs699; Bradykinin Receptor B2, BDKRB2 rs1799722; Peroxisome Proliferator-Activated Receptor Alpha, PPARA rs4253778; Peroxisome Proliferator-Activated Receptor Gamma Co-Activator 1-Alpha, PPARGC1A rs8192678; Thyrotropin Releasing Hormone Receptor, TRHR rs7832552 and Vascular Endothelial Growth Factor, VEGF rs1870377,were calculated and assigned with strength-power and endurance quality. Pearson correlation analysis was employed to investigate the correlation between TGS, and magnitude of physical performances change following intervention. Result: There is a significant correlation between strength-power TGS with lower body muscular strength (r= .65, p<.01) and power (r= -.69, p<.01) following moderate intensity resistance training. Conclusion: In this study, it is demonstrated that participants with higher strength-power TGS, gained greater lower body strength improvement and lesser muscular power decrement even with moderate intensity as compared to high intensity resistance training. Therefore, personalising training based on athlete’s genetic profile may optimise performance.

Development of a genetic risk score for obesity predisposition evaluation.

Obesity is a major public health issue resulting from an interaction between genetic and environmental factors. Genetic risk scores (GRSs) are useful to summarize the effects of many genetic variants on obesity risk. In this study, we aimed to assess the association of previously well-studied genetic variants with obesity and develop a genetic risk score to anticipate the risk of obesity development in the Iranian population. Among 968 participants, 599 (61.88%) were obese, and 369 (38.12%) were considered control samples. After genotyping, an initial screening of 16 variants associated with body mass index (BMI) was performed utilizing a general linear model (p < 0.25), and seven genetic variants were selected. The association of these variants with obesity was examined using a multivariate logistic regression model (p < 0.05), and finally, five variants were found to be significantly associated with obesity. Two gene score models (weighted and unweighted), including these five loci, were constructed. To compare the discriminative power of the models, the area under the curve was calculated using tenfold internal cross-validation. Among the studied variants, ADRB3 rs4994, FTO rs9939609, ADRB2 rs1042714, IL6 rs1800795, and MTHFR rs1801133 polymorphisms were significantly associated with obesity in the Iranian population. Both of the constructed models were significantly associated with BMI (p < 0.05) and the area under the mean curve of the weighted GRS and unweighted GRS were 70.22% ± 0.05 and 70.19% ± 0.05, respectively. Both GRSs proved to predict obesity and could potentially be utilized as genetic tools to assess the obesity predisposition in the Iranian population. Also, among the studied variants, ADRB3 rs4994 and FTO rs9939609 polymorphisms have the highest impacts on the risk of obesity.

Dynamics of body weight during lifestyle modification in patients with high cardiovascular risk, depending on the carriage of various variants of thrifty genes

Objective — to study the relationship between the carriage of polymorphic variants PPARG2 (Pro12Ala), ADRB2 (Gln27Glu), ADRB2 (Agr16Gly), ADRB3 (Trp64Agr), FABP2 (Thr54Ala) and changes in anthropometric parameters under the influence of increased physical activity in individuals with high cardiovascular risk.&#x0D; Materials and methods. In total, 205 people were examined during the period of years 2019 — 2021. Patients were advised to use physical activity frequently in the form of regular exercises. Among patients who passed the 2nd observation point, 60.5 % (124 patients) reported that they expanded their physical activity, 39.5 % (81 patients) began regular exercises. The study included patients with high cardiovascular risk. The International Physical Activity Questionnaire (IPAQ) was used to assess physical activity. Assessments included anthropometric parameters (weight, height, body mass index, waist and hip circumference, body composition (Composition Monitor BF511, Omron, China, 2015)), levels of total cholesterol, triglycerides, low‑density lipoproteins. Muscle strength (kg/cm2) was assessed using an electric dynamometer on the wrist Camry EH101 2013 (2018). Isolation and purification of DNA from the whole blood was carried out using a set of reagents «DNA‑sorb‑B» (Amplisens, RF) according to the manufacturer’s instructions. Amplification of DNA and genotyping at polymorphic sites in the genes PPARG2, ADRB2, ADRB3, FABP2 was performed by real‑time PCR using a set of reagents «SNP‑EXPRESS‑SHOT» («Litech», RF) according to the manufacturer’s instructions using the product detection system real‑time CFX96 Touch (BioRad Laboratories Pte.Ltd.).&#x0D; Results. Depending on the changes in anthropometric parameters, patients were divided into 2 subgroups: in subgroup 1 there was no decrease in BMI before 30.69 ± 7.25 kg/m2, after 29.03 ± 6.84 kg/m2; p = 0.436, and in subgroup 2 a significant decrease in BMI before 31.85 ± 3.68 kg/m2, after 26.79 ± 3.91 kg/m2; p = 0.041. It was revealed that the decrease in BMI in subgroup 2 was accompanied by a statistically significant decrease in the proportion of adipose tissue (р = 0.011) and an increase the proportion of muscle tissue (р = 0.030). In both groups, blood pressure significantly decreased. Heart rate (HR) decreased in both groups, but these changes did not reach statistical significance (p = 0.43). Changes in anthropometric parameters were not accompanied by significant changes in total cholesterol, LDL cholesterol, triglycerides levels. A significant increase in HDL cholesterol levels was revealed. It was found that patients with CC and GG variants of the polymorphic locus PPARG2 (Pro12Ala), CG and GG variants of the polymorphic locus ADRB2 (Gln27Glu) and TT variant of the polymorphic locus ADRB3 (Trp64Agr) prevailed in group 2. No significant differences were found for the FABP2 locus (Thr54Ala). In subgroup 1, there were no significant differences in people with various polymorphic variants of genes.&#x0D; Conclusions. Associations have been established between the carriage of CG/CG + GG PPARG2 (rs1801282), AA/AA + AG ADRB2 (rs1042713) and TT ADRB3 (rs4994) and a decrease in body mass index during exercise expansion in individuals with high cardiovascular risk.&#x0D;

Associations of molecular genetic predictors of type 2 diabetes mellitus with hyperglycemia in extremely low birth weight infants

Hyperglycemia in premature newborns is an independent risk factor for death, so blood glucose testing is widely used in the practice of neonatal intensive care units.Objective: to evaluate the associations of the frequency of carriage of allelic variants of polymorphic loci of genes predisposing to type 2 diabetes mellitus in newborns with extremely low body weight and hyperglycemia.Methods. The study design is prospective, controlled, single – center, non-randomized. Genomic DNA samples were studied in newborn infants with extremely low body weight (ELBW) (n = 105). Previously, we compared the distribution of allele frequencies of the studied genes between a group of newborns with ELBW and a population sample of adults (control). Then, the distribution of allele frequencies of the genes was compared depending on the presence of hyperglycemia in newborns with ELBW. For the analysis, loci with already known association with the development of type 2 diabetes mellitus were selected ‒ ADRB2 (rs1042713) and (rs1042714), ADRB3 (rs4994), GNB3 (rs5443), PPARA (rs4253778), PPARD (rs2016520), TCF7L2_IVS3 (rs7903146) and TCF7L2_IVS4 (rs12255372), PPARGC1A (rs8192678), MTHFR (rs1801131), PPARG (rs1801282), MTNR1B (rs10830963), SIRT1 (rs7069102).Results. In newborns with ELBW, we found a more frequent occurrence of the mutant allele A of the polymorphic locus rs8192678 in the PPARGC1A gene and the allele C of the polymorphic locus rs4253778 in the PPARA gene, in contrast to the adult population sample. But in newborns with ELBW, hyperglycemia is most likely associated with the carrier of the allele C rs1801282 of the PPARG gene (χ2 = 18.972, p &lt; 0.001) and the allele T rs7903146 in the TCF7L2 gene (χ2 = 11.496, p &lt; 0.001).Conclusions. The carriage of the allele С rs1801282 of the PPARG gene is characterized by the presence of a strong conjugation with hyperglycemia in newborns with extremely low body weight. It is desirable to monitor the level of glycemia in the conditions of neonatal intensive care units, taking into account the carriage of genes predisposing to hyperglycemia.

Association of FTO, ABCA1, ADRB3, and PPARG variants with obesity, type 2 diabetes, and metabolic syndrome in a Northwest Mexican adult population

To identify associations among allelic variants of the genes FTO, ABCA1, ADRB3, and PPARG with anthropometric and biochemical traits, metabolic diseases (obesity, T2D or metabolic syndrome) in an adult population from Northwest Mexico. Blood samples were collected from 846 subjects including 266 normal weight subjects, 285 with obesity, and 295 with T2D. Of the 846 persons in the study, 365 presented metabolic syndrome diagnostic criteria. Anthropometric and biochemical traits were recorded and 4 single nucleotide polymorphisms (SNPs): FTO rs9939609 A-allele, ABCA1 rs9282541 A-allele, ADRB3 rs4994 G-allele, and PPARG rs1801282 G-allele were genotyped by real-time PCR. FTO rs9939609 A-allele was significantly associated with obesity (p: 8.3×10-4), and metabolic syndrome (p: 0.001), but no individual SNPs were significantly associated with T2D. Finally, the cumulative risk of the four SNPs was significantly associated with obesity (p: 1.95×10-4). Associations in FTO, ABCA, ADRB3, and PPARG SNPs presented in this study with obesity and metabolic syndrome could represent a risk for developing metabolic diseases in Northwest Mexican adult subjects.

Prediction and Identification of Power Performance Using Polygenic Models of Three Single-Nucleotide Polymorphisms in Chinese Elite Athletes.

Objective: The manuscript aims to explore the relationship between power performance and SNPs of Chinese elite athletes and to create polygenic models. Methods: One hundred three Chinese elite athletes were divided into the power group (n = 60) and endurance group (n = 43) by their sports event. Best standing long jump (SLJ) and standing vertical jump (SVJ) were collected. Twenty SNPs were genotyped by SNaPshot. Genotype distribution and allele frequency were compared between groups. Additional genotype data of 125 Chinese elite athletes were used to verify the screened SNPs. Predictive and identifying models were established by multivariate logistic regression analysis. Results: ACTN3 (rs1815739), ADRB3 (rs4994), CNTFR (rs2070802), and PPARGC1A (rs8192678) were significantly different in genotype distribution or allele frequency between groups (p < 0.05). The predictive model consisted of ACTN3 (rs1815739), ADRB3 (rs4994), and PPARGC1A (rs8192678), the area under curve (AUC) of which was 0.736. The identifying model consisted of body mass index (BMI), standing vertical jump (SVJ), ACTN3, ADRB3, and PPARGC1A, the area under curve (AUC) of which was 0.854. Based on the two models, nomograms were created to visualize the results. Conclusion: Two models can be used for talent identification in Chinese athletes, among which the predictive model can be used in adolescent athletes to predict development potential of power performance and the identifying one can be used in elite athletes to evaluate power athletic status. These can be applied quickly and visually by using nomograms. When the score is more than the 130 or 148 cutoff, it suggests that the athlete has a good development potential or a high level for power performance.

Nomograms For Predicting And Identifying Polygenetics Models Of Power Performance In Chinese Elite Athletes

Based on the single nucleotide polymorphism(SNP) of elite power performance athletes, combined with other related phenotypic indicators, models for predicting and identifying the power performance of Chinese elite athletes was established, and the models were visualized by the method of nomogram. PURPOSE: To explore the relationship between power performance and SNP of Chinese elite athletes and to creat polygenic models for predicting and identifying elite power performance. METHODS: 103 elite athletes (age=24.3±3.2years; height=174.9±8.4cm; body mass=66.3±14.0kg; body mass index (BMI)=21.5±3.4) which were all Chinese were divided into power group(n=60) and endurance group(n=43) by their sport event. Best standing long jump (SLJ) and standing vertical jump (SVJ) were collected. Saliva samples were collected to test and 20 SNPs were genotyped by SNaPshot. test was used to compare the genotype distribution and allele frequency between groups. Predicting and identifying models were established by multivariate logistic regression analysis. Nomograms were created to visualize. RESULTS: ACTN3(rs1815739),ADRB3(rs4994) and PPARGC1A(rs8192678) were significant both in genotype distribution and allele frequency between groups(P<0.05). The predicting model was consisted of ACTN3(rs1815739) (OR=2.448, 95% CI: 1.277-4.693), ADRB3(rs4994) (OR=3.546, 95% CI: 1.360-9.245) and PPARGC1A(rs8192678) (OR=2.159, 95% CI: 1.109-4.207), the AUC of which was 0.736. The identifying model was consisted of BMI(OR=1.217, 95% CI: 1.005-1.473), SVJ(OR=1.092, 95% CI: 1.040-1.146), ACTN3(OR=2.127, 95% CI: 1.006-4.497), ADRB3(OR=5.029, 95% CI: 1.451-17.427) and PPARGC1A(OR=2.370, 95% CI: 1.070-5.250), the AUC of which was 0.854. Based on the two models, nomograms were created to visualize the results. CONCLUSION: Two models can be both used for talent identification in Chinese athletes, among which the predicting one can be used in adolescent athletes to predict the development potential of power performance and the identifying one can be used in elite athletes to distinguish and evaluate power athletic status. It can be applied quickly and visually by using the method of nomogram. Supported by key basic research grants from Science and Technology Commission of Shanghai Municipality, GrantNo.16JC1400500.

The relationship between PNP, GSTO-1, AS3MT and ADRB3 gene polymorphisms and urinary arsenic concentration among copper smelter and refinery employers.

The aim of this study was to assess the relationship between polymorphisms of genes encoding enzymes involved in arsenic metabolism and urinary arsenic concentration in people occupationally exposed to arsenic. The data from 113 employers directly exposed to lead, cadmium, and arsenic in copper smelter in Legnica and Glogow were collected. Urinary arsenic concentration was measured. In addition, blood level of cadmium, lead, and zinc protoporphyrins was assayed. Genetic analyses included polymorphism of PNP (rs 1130650), GSTO-1 (rs 4925), AS3MT (rs 11191439), and ADRB3 (rs4994) genes. Individuals occupationally exposed to arsenic compounds, who have allele T in homozygous constellation in locus rs 1130650 of PNP gene, are predisposed to lower urinary arsenic concentration, while AA homozygosity in locus rs 4925 of GSTO-1 gene may result in statistically significant higher urinary arsenic concentration. Polymorphisms of AS3MT and ADRB3 genes showed no statistically significant correlation with urinary arsenic, however, there was a tendency to higher arsenic concentration in allele A carriers in locus rs4994 of ADRB3 gene and in allele T carriers in rs 11191439 of AS3MT gene. This study indicates that arsenic absorption and metabolism depend on polymorphisms of genes encoding PNP and GSTO-1. Individuals with disadvantageous constellation of polymorphisms are more susceptible to harmful effects of arsenic exposure.

Beta-3-adrenergic Receptor rs4994 Polymorphism Is a Potential Biomarker for the Development of Nonalcoholic Fatty Liver Disease in Overweight/Obese Individuals.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. Obesity is the most common and well-established risk factor for NAFLD, but there are large interindividual differences in the relationship between weight status and the development of NAFLD. Beta-3-adrenergic receptor (ADRB3) plays a key role in the development of visceral obesity and insulin resistance; however, the effect of ADRB3 polymorphisms on the risk of NAFLD remains unclear. We investigated whether or not a common rs4994 polymorphism (T190C) in the ADRB3 gene is associated with the risk of NAFLD through an increase in the body mass index (BMI) among the general population. We performed cross-sectional and longitudinal analyses in a total of 591 Japanese health screening program participants. Among the overweight or obese subjects, but not normal-weight subjects, individuals with the C/C genotype had a higher risk of developing NAFLD in comparison to those with other genotypes in the cross-sectional analysis (odds ratio: 4.40, 95% confidence interval (CI): 1.08–17.93). Meanwhile, the receiver operating characteristic curve indicated that the association between an increase in the BMI and the presence of NAFLD in subjects with the C/C genotype (area under the curve: 0.91, 95% CI: 0.78–1.00) was more pronounced in comparison to subjects with other genotypes. These above-described findings were verified by the analyses using a replicated data set consisting of 5,000 random samples from original data sets. Furthermore, among the 291 subjects for whom longitudinal medical information could be collected and who did not have NAFLD at baseline, the Cox proportional hazard model also confirmed that overweight or obese status and the C/C genotype were concertedly related to the increased risk of NAFLD development. These results suggest that genotyping the ADRB3 rs4994 polymorphism may provide useful information supporting the development of personalized BMI-based preventive measures against NAFLD.

Associations of polymorphisms of the FTO, ADRB3, LEPR genes with obesity and the impact on Them of a complex of recreational activities among residents of the North Caucasus

Annotation Objective To study the effect of a comprehensive health program on the effectiveness of reducing overweight depending on the carriage of allelic variants and FTO (rs9939609), ADRB3 (rs4994) and LepR (rs1137101) genotypes among residents of the North Caucasus. Materials and methods Gene polymorphisms were analyzed by the SNP-method with allele-specific primers on the test systems of ‘Litex’ Research and Production Company (RPC). The frequencies rs9939609, rs4994 and rs1137101 were studied in individuals with overweight, I-III degrees of obesity (n = 120) compared with the control group (n = 42). Experimental data were processed in the program SPSS Statistics 22.0. A comprehensive wellness program (CWP), along with health improving measures, limits caloric intake to 800–1200 kcal per day and excludes animal fats and proteins. The body mass index (BMI) of the examined individuals was calculated by the Ketle method as the ratio of body weight (kg) to height (m2). In accordance with WHO criteria (1997), the severity of overweight varies in the ranges of values: normal weight – 18–24.9 kg/m2; overweight – 25–29.9 kg/m2; I degree obesity – 30–34.9 kg/m2; II degree obesity – 35–39.9 kg/m2; III degree obesity – 40 and more kg/m2. Results A significant increase in rs9939609 (p = 0.003), rs4994 (p = 0.0001) was found in the group of patients when compared with the control. The 64Arg allele (р = 5.0E-6) and the Arg64Arg genotype (p = 0.0001) of the ADRB3 gene have the greatest prognostic significance for the diagnosis of obesity, increasing the risk by 10 and 17 times, respectively. Significant differences in the distribution of FTO gene polymorphism were established to a lesser extent and only by the T23525T genotype (χ2 = 7.20; р = 0.03). However, the correlation analysis revealed a number of strong positive connections for the T23525T FTO genotype between the ratio of visceral fat (r = +0.541; p = 0.01), fat (r = +0.548; p = 0.01) and muscle mass (r = +0.587; p = 0.01). It should be noted that with SNP-typing of three polymorphic variants of the FTO, ADRB3 and LepR genes, the transversion phenomenon was established by rs9939609 in 26 out of 120 participants (21.6%). Conclusion According to the obtained data, we confirmed the promising use of rs9939609, rs4994 as genetic markers of obesity. The discovered phenomenon of transversion of polymorphisms in the FTO gene under the influence of the complex health program does not exclude a multi-level regulation of reparation processes and epigenetic activation of genes, which requires further study.

Genotyping Method and Frequency of ADRB3-rs4994 Single Nucleotide Polymorphism Genotypes in Hanoi 3-5 Years Old Chidren

Genotyping Method and Frequency of ADRB3-rs4994 Single Nucleotide Polymorphism Genotypes in Hanoi 3-5 Years Old Chidren

Изучение ассоциации полиморфизма генов со спортивной успешностью и риском развития алиментарно-зависимых заболеваний у спортсменов, представляющих циклические виды спорта

The studies of genetic polymorphisms rs1815739 (ACTN3 gene), rs2016520 (gene PPARD), rs1042713 (ADRB2 gene), rs1799945 (HFE gene), rs1801282 (PPARG gene) of athletes involved in cyclic sports were carried out. Genotyping was performed using allele-specific amplification with real-time detection of results and the use of TaqMan probes. As a result of the research, a higher incidence of alleles associated with endurance (T-polymorphism rs1815739 and G - polymorphism rs2016520) was revealed in athletes of cyclic sports. The analysis of the results of genetic polymorphisms: rs9939609 gene FTO, ADRB3 rs4994 gene rs2228570 and VDR gene showed that the risk of development of alimentary-related diseases (obesity and osteoporosis) in the examined athletes after sports career is lower than in the General population.

Non-Synonymous Single-Nucleotide Polymorphisms and Physical Activity Interactions on Adiposity Parameters in Malaysian Adolescents.

Several non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia. We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model. PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF. Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.

Association of β3-adrenergic receptor rs4994 polymorphisms with the risk of type 2 diabetes: A systematic review and meta-analysis.

The association of ADRB3 polymorphism with the risk of T2DM remains unclear perhaps due to different ethnicities and small study sizes. We systemically evaluated the association of β3-adrenergic receptor(ADRB3)rs4994 and type 2 diabetes(T2DM) by pooling all of the case-control studies reported, and also elucidated the association according to the ethnicity and obesity of the subjects. A literature search was conducted using PubMed, EMBASE, Cochrane Library, Korean scientific database, Chinese medical databases, and the Indian medical database to identify eligible studies for determining the association of ADRB3 rs4994 and T2DM risk. The association was examined in five genetic models: the allelic(AG), recessive(RG), dominant(DG), homozygous(HMG), and heterozygous(HTG) genetic models. Subgroup analyses stratified by ethnicity(Asians and others) were assessed. This meta-analysis included 17 eligible studies meeting Hardy-Weinberg equilibrium consisting of 4864 patients with T2DM(cases) and 8779 people without diabetes(controls). All models had no heterogeneity or publication bias in the meta-analysis including all subjects. ADRB3 rs4994 polymorphism of all subjects was significantly associated with an increased risk of T2DM in all genetic models with random effects: AG(OR=1.18, 95% CI: 1.05-1.32), RG(OR=1.76, 95% CI: 1.27-2.42), DG(OR=1.16, 95% CI: 1.03-1.30), HMG (OR=1.78, 95% CI: 1.25-2.52), and HTG(OR=1.11, 95% CI: 1.01-1.23). Furthermore, in sub-group analysis all models except HTG exhibited significant associations between T2DM and ADRB3 in Asians. However, the non-Asian group had no significant association in any genetic models with random effects. Middle-age adult Asians with the ADRB3 rs4994 minor alleles are at increased risk of T2DM.

A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.

Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

Полиморфизм генов бета-адренорецепторов и риск эссенциальной гипертензии

The aim of the current study was to analyse an association between ADRB1, ADRB2 и ADRB3 gene variants and essential hypertension (EH) in the ethnic group of Tatars residing in the Republic of Bashkortostan (Russian Federation). Design and methods . We performed genotyping of ADRB1 rs1801252, ADRB2 rs1042713 and ADRB3 rs4994 polymorphisms using polymerase-chain reaction with allele-specific primers in the study group consisting of 530 individuals (216 hypertensive patients, 314 controls). Considering the fact that gender is a major risk factor for the development of hypertension before age 45, the study group was composed of male individuals. Results. We detected an association between ADRB2 rs1042713 and EH. ADRB2*A/G genotype was found to be associated with an increased risk of EH (odds ratio, OR = 1,68; p = 0,004); ADRB2*G/G genotype, on the contrary, was shown to be protective against the disease (OR = 0,58; p = 0,01). ADRB2*A/G genotype also marked an increased risk of hypertension in patients with obesity (OR = 3,01; P = 0,01), while ADRB2*G/G genotype carriers with body mass index > 30 kg/m 2 had lower risk of EH (OR = 0,29; P = 0,01) when compared to the control individuals of the same category. Conclusion. Our study has shown that ADRB2 rs1042713 polymorphism is associated with the risk of EH, and the effect is more pronounced in individuals with obesity.