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
-
Serum Vitamin E (α-Tocopherol) Estimation: A Potential Biomarker of Antioxidant Status Evaluation on Heavy Metal Toxicities
Recent Patents on Biomarkers Ouabain Antagonists as Antihypertensive Agents
Current Pharmaceutical Design Support and Social Contact as a Decisive Meta-Variable in Morbidity and Social Welfare of the Older Person
Current Aging Science Overcoming Resistance to EGFR Inhibitors in NSCLC
Reviews on Recent Clinical Trials Synthetic Methods for the Preparation of Triazepandiones and Review of their Applications
Current Organic Chemistry Preoperative Pulmonary Assessment: A Review
Current Respiratory Medicine Reviews Abnormal Insulin Signaling: Early Detection of Silent Coronary Artery Disease-Erectile Dysfunction?
Current Pharmaceutical Design Inhibition of RAGE Axis Signaling: A Pharmacological Challenge
Current Drug Targets Preface [Hot Topic: Treatment of Hypertension, Its Pathophysiology and the Clinical Use of Antihypertensive Drugs (Executive Editor: Gregory Y.H. Lip)]
Current Pharmaceutical Design Nimodipine Reappraised: An Old Drug With a Future
Current Neuropharmacology Coenzyme Q10 Reduction with Statins: Another Pleiotropic Effect
Current Drug Therapy Contrast Echocardiography: An Update on Clinical Applications
Current Pharmaceutical Design Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) FTIR Spectroscopy to Study Bioeffects of Static Magnetic Fields on Neuronal-like Cell Cultures
Current Metabolomics Human Liver Enzymes Responsible for Metabolic Elimination of Tyramine, a Vasopressor Agent from Daily Food
Drug Metabolism Letters The Roles of β-Carotene in Cardiomyocytes
Current Nutrition & Food Science Sex, Stress and their Influence on Respiratory Regulation
Current Pharmaceutical Design History and Global Status of the New Coronavirus Covid-2019 and Aspects of Previous Infections of SARS-CoV and MERS-CoV: A Systematic Review
Coronaviruses Current and Emerging Therapies in Primary Myelofibrosis
Cardiovascular & Hematological Disorders-Drug Targets Can We Move Forward After ADVANCE?
Vascular Disease Prevention (Discontinued)