Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GNB3 825T allele encodes a product that has enhanced activation of heterotrimeric G proteins in vitro and could play a role in adipogenesis. We therefore evaluated the possibility that the GNB3 825T allele was associated with obesity in a sample of 213 healthy Canadian Inuit. We found that body weight, body mass index, waist girth, hip girth, subscapular skinfold thickness, and triceps skinfold thickness were significantly higher in subjects with the GNB3 825T/T genotype than in subjects with other genotypes. Furthermore, two anthropometric ratios, namely that of waist to hip circumference and that of subscapular to triceps skinfold thickness, were not significantly different across genotypes. This suggested that the increased deposition of fat in subjects with the GNB3 825T/T genotype was generalized and not localized to particular subregions. There was no association of this genetic variation with blood pressure. The GNB3 825T/T genotype accounted for between 1.6% and 3.3% of the total variation (< or =13% of attributable variation) of the obesity-related traits. The potential for a genetic marker of obesity creates opportunities for future studies in the Inuit, not just to confirm the associations, but also to examine prospectively the influence of interventions and possible relationships between GNB3 825T and longer term complications of obesity.
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PMID:G-protein beta3 subunit gene splice variant and body fat distribution in Nunavut Inuit. 1052 25

Following a classical candidate gene approach we have detected a C825T polymorphism in the gene GNB3 which encodes the G beta 3 subunit of heterotrimeric G proteins. The 825T allele causes alternative splicing of the gene and the generation of a truncated but functionally active splice variant of G beta 3 which is referred to as G beta 3s. Thus, genotyping for the C825T polymorphism is predictive for the activation of certain G proteins in humans. The 825T allele is significantly associated with an increased risk for hypertension in Caucasians, most likely "low renin hypertension" and it accumulates significantly in individuals with a strong family history of hypertension. Highest frequencies of the 825T allele (up to 80%) are found in old ethnicities, e.g. black Africans, African Americans, bushmen, and Australian aborigines. This suggests that enhanced G protein activation represents a thrifty genotype which might have facilitated survival in our ancestors. Frequencies of the 825T allele are significant lower in Asians (approximately 40 to 50%) and Caucasians (30%). More recent studies show that young 825T allele carriers are predisposed for obesity and this association could be confirmed across different ethnicities including young Germans, as well as Chinese and black African individuals. Thus, genotyping at the GNB3 locus represents an ideal tool for preventive medicine in that individuals at risk for obesity and hypertension can be identified early and counteract their genetic predisposition through changes in lifestyle. In individuals with borderline hypertension genotyping can facilitate the decision for medical treatment as a positive test result confirms an inherited form of hypertension.
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PMID:[Genetic polymorphism of the G-protein beta3 subunit, obesity and essential hypertension]. 1071 7

For diagnosing cardiovascular emergencies, cardiologists mainly rely on physiological examinations. Biochemical laboratory examinations can facilitate emergency diagnosis and genetic diagnosis can facilitate a fundamental understanding of cardiovascular diseases. Recent progress in biochemical examinations for cardiovascular diseases includes measurement of troponin T, heart type fatty acid-binding protein, and LDL-cholesterol. Recent progress in genetic examinations includes analysis of mitochondrial DNA, obesity-related genes and single nucleotide polymorphisms. A safe and convenient system of collecting, transporting, and storing blood and other biological specimens, and the subsequent purification of genomic DNA from the stored specimens is available. Therefore, busy doctors and staff of clinical laboratory can plan subsequent DNA examinations without causing concern and pain. A recently reported human mutation of heterotrimeric G protein beta 3 subunit produces a gain-of-function G protein signaling abnormality. A common polymorphic base substitution, C825T, in the GNB3 gene is associated with an aberrantly spliced transcript lacking 123 nucleotides. A significant association of the T allele with essential hypertension or obesity has been suggested.
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PMID:[Progress in biochemical and genetic examinations in clinical laboratory of cardiovascular diseases]. 1080 12

The 825T allele of the gene GNB3 which encodes the beta 3 subunit of heterotrimeric G proteins is associated with enhanced signal transduction via G proteins through the generation of a splice variant termed Gbeta3s. It was detected following a classical candidate gene approach using cell lines from patients with enhanced signal transduction and essential hypertension. The high frequency of the 825T allele in 'old' ethnicities, e.g. bushmen and Australian aborigines as well as in black populations, together with its strong association with obesity suggests that the 825T allele is a true 'thrifty genotype'. Development of obesity associated with the 825T allele is strongly influenced by lifestyle, e.g. physical activity, and other exogenous influences like pregnancy. In hypertension the 825T allele is associated with low renin activity and appears to strongly predict the development of left ventricular hypertrophy. In type 2 diabetes the 825T allele was reported to be predispose for end-stage renal disease, whereas this effect has not yet been confirmed for patients with type 1 diabetes.
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PMID:G protein beta 3 subunit 825T allele, hypertension, obesity, and diabetic nephropathy. 1139 Jul 42

The GNB3 825C/T polymorphism, which is common worldwide, is associated with enhanced G-protein activation. The frequency of 825-T allele was increased with body mass index (BMI) and finally had a high frequency in relatively mild obese (BMI >27 kg/m(2)) subjects in some populations. In the present study, we investigated 208 severely obese [BMI >or=30 kg/m(2) (97th percentile)] Japanese subjects including 146 probands with diabetes. No increase in the 825-T allele frequency was observed in the 208 severely obese and even in a subgroup of the 55 most obese [BMI >or=35 kg/m(2) (99.7th percentile)] subjects compared with that in 150 controls (BMI <25 kg/m(2)) (0.48 and 0.48 vs 0.51, respectively). Also, the frequency was not increased in the 146 obese subjects with diabetes (0.48). We concluded that the 825-T allele is not associated with obesity or diabetes associated with obesity at least in the Japanese population.
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PMID:Analysis of 825C/T polymorphism of G proteinbeta3 subunit in obese/diabetic Japanese. 1152 49

The 825-C/T polymorphism of the beta 3 subunit of the heterotrimeric G protein gene (GNB3) has been shown to be associated with essential hypertension in humans. Recently, it was also reported that the 825-T allele has a higher frequency in obese than non-obese hypertensives suggesting that the primary effect of this allele is on body weight. The association to hypertension might merely be a secondary effect of the higher weight of the respective allele carriers. To investigate an involvement of the 825-T allele in body weight regulation in young individuals, we evaluated allele frequencies in 440 extremely obese children and adolescents (82.9% had a body mass index [BMI] > or = 99th percentile), 51 obese students (BMI > or = 90th percentile), 110 normal weight students (BMI between 40th and 60th percentile) and 144 underweight students (BMI < or = 15th percentile). The study groups were genotyped by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). The one-sided Yates-corrected chi(2)-test and the Cochran-Armitage trend test for association were performed. Tests for association were negative. The 825-T allele frequencies were similar in the four study groups belonging to different weight ranges (extreme early onset obesity: 0.29; obesity: 0.28; normal weight: 0.35; underweight: 0.32). Similarly, genotype frequencies did not differ between the groups. We concluded that the 825-T allele of the GNB3 does not play a major role in weight regulation in German children, adolescents and young adults.
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PMID:No evidence for involvement of alleles of the 825-C/T polymorphism of the G-protein subunit beta 3 in body weight regulation. 1174 88

Using a classical candidate gene approach, we have described a common C825T polymorphism in the gene GNB3 which encodes the ubiquitously expressed beta3 subunit of heterotrimeric G proteins. The 825T allele is associated with alternative splicing of the gene and the formation of a truncated but functionally active beta3 subunit which is referred to as Gbeta3s. Expression of the splice variant results in an enhanced G protein activation on stimulation of G protein-coupled receptors. Carriers of the 825T allele show an increased risk for hypertension and left ventricular hypertrophy. Homo- and heterozygous 825T allele carriers respond with a stronger decrease in blood pressure to therapy with a thiazide diuretic than homozygous 825C allele carriers. Moreover, 825T allele carriers appear to have an increased risk for obesity which appears sensible given the established role of G protein signaling in adipogenesis. The highest frequencies of the 825T allele are found in ethnicities with the highest lifestyle-dependent risk for obesity, e.g., black Africans and East Asians. This suggests that the 825T allele fulfills the criteria of a thrifty genotype.
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PMID:Molecular genetics of G proteins and atherosclerosis risk. 1177 79

The 825T-allele of the gene GNB3 encoding the G protein beta3 subunit is associated with hypertension and obesity, and identifies individuals highly responsive to diuretic therapy. Gbeta3s, a Gbeta3 protein variant generated by alternative splicing in carriers of the 825T-allele, is linked to increased signal transduction and is a potential cause for the observed pathophysiology. Here, we searched the entire GNB3 gene for additional polymorphisms and analysed their prevalence in Caucasian, black African and Asian populations. We detected six novel single nucleotide polymorphisms which were termed according to their location as G76A, G1906T, G2906A, A3882C, G5177A, and G5249A. Furthermore, we found a CACA-insertion-deletion polymorphism at position 6496. Genotyping and association studies resulted in the definition of two major GNB3 haplotypes, termed 'C-haplotype' (alleles 825C, 3882A, 5249G, 6496CACA-) and 'T-haplotype' (alleles 825T, 3882C, 5249A, 6496CACA+). Molecular modelling studies revealed that the pre-mRNA structures of both haplotypes exhibit marked differences which may account for the alternative splicing predominantly observed with the T-haplotype. The prevalence of these haplotypes in major ethnic populations differs considerably. Furthermore, we detected additional frequent GNB3 polymorphisms. These variants were restricted to one or two major ethnic populations. Our results will aid future studies on population-specific effects of the GNB3 variants on risk and course of frequent diseases, including hypertension, obesity, stroke and myocardial infarction. Furthermore, they will contribute to the understanding of GNB3-related population-specific pharmacogenetic differences in the response to major drugs, as already shown for diuretics and antidepressants.
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PMID:Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit. 1192 36

The recently discovered C825T polymorphism of the G-protein beta 3 subunit has been reported to be associated with the development of hypertension and obesity. The aim of our study was to investigate the relationship between the C825T polymorphism and functional aspects of human adipose cells, particularly with regard to adipose differentiation and lipolysis. Adipose tissue samples were collected from 65 women with a BMI ranging from 19.7 to 39.7 kg/m 2 undergoing surgical mammary reduction. The stromal cells were allowed to undergo differentiation in primary culture using adipogenic media of defined composition. No significant difference was observed between the CC carriers and the carriers of the T allele under all adipogenic conditions with differentiation capacity related to the genotype. In a subgroup of patients (n = 20), lipolysis in isolated fat cells was determined by measurement of glycerol in the culture medium upon catecholamine exposure. Glycerol release after 10(-7) mmol/l isoproterenol was significantly higher in fat cells from the 10 CC carriers than in adipocytes from the T allele carriers when expressed as percentage of basal glycerol release (increase above baseline: CC: 809 +/- 174 %, T allele carriers: 247 +/- 88 %, p = 0.01), while basal glycerol concentrations were no different according to genotype after controlling for either age or BMI. In conclusion, this study provides the first evidence that the GNB3 825T allele is associated with an impairment of the beta-adrenergic control of lipolysis.
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PMID:Effects of the G-protein beta3 subunit 825T allele on adipogenesis and lipolysis in cultured human preadipocytes and adipocytes. 1238 23

The GNB3 C825T gene polymorphism has recently been identified and associated with hypertension, obesity and left ventricular hypertrophy. The aim of the study was to determine the relationship between the C825T polymorphism of the gene encoding for the G protein beta3 subunit (GNB3 C825T) and vascular hypertrophy. We studied a cohort of 306 subjects (age 49 +/- 12 years) without evidence of cardiovascular disease and never treated with cardiovascular drugs. Vascular phenotypes were evaluated for the common carotid and radial arteries using high-resolution echo-tracking devices. Genotype frequencies were in agreement with the Hardy-Weinberg equilibrium. For the radial artery, mean wall thickness was significantly higher in subjects carrying the 825T allele than in CC genotype subjects (240 +/- 54 microm for CT genotype and 241 +/- 53 microm for TT genotype vs. 222 +/- 52 microm for CC genotype, p = 0.01). The frequency of the 825T allele was significantly different in subjects with (52%) and without (35%) radial artery hypertrophy (chi(2) = 10.88, p < 0.001). The relative risk of radial artery hypertrophy in subjects carrying the 825T allele compared with those with the CC genotype was 3.02 (95% CI 1.53- 5.95). A logistic regression analysis indicated that the positive and significant association between the 825T allele and radial artery hypertrophy was independent of age, blood pressure, gender and BMI. In contrast, no association between genotypes and carotid artery wall thickening was observed. These results suggest that some genetic characteristics determine in part the patterns of radial artery geometrical changes. As the 825T allele is associated with vascular hypertrophy of a muscular artery but not with structural changes of an elastic artery, we hypothesize that the 825T allele may be a genetic marker of arteriolosclerosis.
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PMID:Association between the G protein beta3 subunit 825t allele and radial artery hypertrophy. 1256 75


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