Abstract
Using a classical candidate gene approach, we have described a common C825T polymorphism in the gene GNB3, encoding the ubiquitously expressed β3 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 Gβ3, referred to as Gβ3s. In addition, the presence of a 825T allele is predictive of an enhanced signal transduction via PTX-sensitive G proteins. Caucasian carriers of the 825T allele show a significantly increased risk for hypertension, most likely “low renin hypertension”, and show an increased response to thiazide diuretics. The 825T allele comes along with an increased renal perfusion and accumulates significantly in the 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. Moreover, there is some evidence for an association with type-2 diabetes and cardiovascular disease. Genotyping at the GNB3 locus may represent an interesting candidate in a preventive medicine because individuals at risk for obesity and hypertension can be identified early and then can counteract their genetic predisposition through changes in lifestyle.
Keywords: Protein, hypertension, GNB3 locus, Thrifty Genotype
Current Genomics
Title: The G Protein β3 Subunit Gene (GNB3) 825T Allele - a Thrifty Genotype
Volume: 4 Issue: 4
Author(s): C. K. Naber, R. Erbel and W. Siffert
Affiliation:
Keywords: Protein, hypertension, GNB3 locus, Thrifty Genotype
Abstract: Using a classical candidate gene approach, we have described a common C825T polymorphism in the gene GNB3, encoding the ubiquitously expressed β3 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 Gβ3, referred to as Gβ3s. In addition, the presence of a 825T allele is predictive of an enhanced signal transduction via PTX-sensitive G proteins. Caucasian carriers of the 825T allele show a significantly increased risk for hypertension, most likely “low renin hypertension”, and show an increased response to thiazide diuretics. The 825T allele comes along with an increased renal perfusion and accumulates significantly in the 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. Moreover, there is some evidence for an association with type-2 diabetes and cardiovascular disease. Genotyping at the GNB3 locus may represent an interesting candidate in a preventive medicine because individuals at risk for obesity and hypertension can be identified early and then can counteract their genetic predisposition through changes in lifestyle.
Export Options
About this article
Cite this article as:
Naber K. C., Erbel R. and Siffert W., The G Protein β3 Subunit Gene (GNB3) 825T Allele - a Thrifty Genotype, Current Genomics 2003; 4 (4) . https://dx.doi.org/10.2174/1389202033490358
DOI https://dx.doi.org/10.2174/1389202033490358 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Combining Bevacizumab with Radiation or Chemoradiation for Solid Tumors: A Review of the Scientific Rationale, and Clinical Trials
Current Angiogenesis (Discontinued) Relationship between Hyperlipidemia, Cardiovascular Disease and Stroke: A Systematic Review
Current Cardiology Reviews Chronopharmaceutics: A Promising Drug Delivery Finding of the Last Two Decades
Recent Patents on Drug Delivery & Formulation Renoprotective Effects of the L-/T-type Calcium Channel Blocker Benidipine in Patients with Hypertension
Current Hypertension Reviews Nerve Growth Factor: Early Studies and Recent Clinical Trials
Current Neuropharmacology Caspases as Drug Targets in Ischemic Organ Injury
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Design and Development of Preservative Free Herbal Dosage Forms
The Natural Products Journal New Perspectives in the Treatment of Cushings Syndrome
Current Drug Targets - Immune, Endocrine & Metabolic Disorders High-Throughput Functional Genomic Methods to Analyze the Effects of Dietary Lipids
Current Pharmaceutical Biotechnology Retinal Vascular Features for Cardio Vascular Disease Prediction: A Review
Recent Patents on Computer Science The Efficacy and Safety of Cilnidipine on Mild to Moderate Essential Hypertension: A Systematic Review and Meta-analysis of Randomized Controlled Trials in Chinese Patients
Cardiovascular & Hematological Disorders-Drug Targets Heme Oxygenase System and Hypertension: A Comprehensive Insight
Current Pharmaceutical Design ACE2 and Diabetic Complications
Current Pharmaceutical Design Non-Infectious Complications of Immunosuppressant Medications in Renal Transplant Patients
Current Clinical Pharmacology Social Determinants of Childhood Obesity: Beyond Individual Choices
Current Pediatric Reviews Role of Oxidative and Nitrosative Stress, Longevity Genes and Poly(ADPribose) Polymerase in Cardiovascular Dysfunction Associated with Aging
Current Vascular Pharmacology Treatment of Early Vascular Ageing
Current Pharmaceutical Design The New Adipose Tissue and Adipocytokines
Current Diabetes Reviews Hyperglycemia-Related Pathophysiologic Mechanisms and Potential Beneficial Actions of Melatonin
Mini-Reviews in Medicinal Chemistry Prodrug Strategies for Antihypertensives
Current Topics in Medicinal Chemistry