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      Transmission of G-Protein β3 Subunit C825T Alleles to Offspring Affected with End-Stage Renal Disease

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          Abstract

          Background: Results of epidemiological studies have suggested that a hereditary predisposition to the development of chronic renal failure exists, and that such predisposition might be independent from underlying etiology of kidney disease. On the other hand, high blood pressure contributes substantially to a faster rate of progression of renal damage, regardless of underlying etiology of kidney disease. In this study we tested whether GNB3 C825T polymorphism, previously reported to be associated with hypertension, contributes to predisposition to end-stage renal disease (ESRD). Methods: GNB3 polymorphism was genotyped in 247 family trios: offspring affected with ESRD and both parents, and transmission/disequilibrium test was used to establish the allele-phenotype association. Among the examined offspring, 47 patients had ESRD in the course of type 1 diabetes and diabetic nephropathy, 120 had primary glomerulonephritis and 80 had interstitial nephritis. We observed no significant differences between the GNB3 C and T allele transmission from heterozygous parents to affected offspring. Results: In the overall group of examined patients, the C:T allele transmission (%) was 48:52, while in patients with diabetic nephropathy, chronic glomerulonephritis and chronic interstitial nephritis the transmission was (%) 50:50, 48:52 and 48:52, respectively. Conclusion: The results of our study suggest that GNB3 C825T polymorphism does not contribute substantially to the increased risk of the development of ESRD.

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          Increased frequency of G-protein beta 3-subunit 825 T allele in dialyzed patients with type 2 diabetes.

          A polymorphism (C825T) in exon 10 of the gene encoding the beta 3 subunit of heterotrimeric G proteins (GN beta 3) has recently been described, and the T allele was found to be associated with late-onset hypertension. Because hypertension is a known risk factor for the development of clinically manifest progressive renal disease, we examined the C825T polymorphism in older hemodialysis patients suffering from nondiabetic renal disease or type 2 diabetes with presumed diabetic nephropathy, respectively, and in older healthy controls.
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            Genes and renal disease.

            The identification of genetic linkage between polymorphic markers and common kidney diseases, including focal and segmental glomerulosclerosis and diabetic nephropathy, clearly demonstrates that inherited factors contribute to renal failure susceptibility. These breakthroughs reveal the powerful contribution that molecular genetic techniques can make in the search for inherited factors that initiate renal failure and lead to its progression. Additionally, the environmental factors predisposing to nephropathy will be more readily detectable when evaluated in genetically similar populations. This manuscript reviews the developments in genetic epidemiology and molecular genetics of chronic renal failure.
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              G-Protein β 3 Subunit C825T Variant, Nephropathy and Hypertension in Patients with Type 2 (Non-Insulin-Dependent) Diabetes mellitus

              Background: There is substantial evidence that hereditary factors contribute to the predisposition to diabetic nephropathy. On the other hand, it has been suggested that genetics of diabetic nephropathy and hypertension may overlap. Recently, a C to T substitution (C825T) in the gene encoding for the guanine-nucleotide-binding protein β 3 subunit (GNB3) was identified, and this molecular variant was found to be associated with enhanced activation of G proteins and increased risk of the development of hypertension. The aim of the study was to test whether GNB3 C825T polymorphism contributes to the development of incipient or overt nephropathy or hypertension in type 2 diabetic patients. Methods: GNB3 genotype was determined in 130 type 2 diabetic patients with overt proteinuria or chronic renal failure, 155 diabetic patients with microalbuminuria and 163 control subjects with normoalbuminuria and known type 2 diabetes duration of at least 10 years. Results: No differences in GNB3 genotype distributions or allele frequencies between the study groups were found. Also, no differences between normotensive and hypertensive patients were demonstrated. Conclusion: The study provided evidence against the major impact of the GNB3 C825T polymorphism on the increased risk of the development of nephropathy or hypertension in type 2 diabetic patients.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                0250-8095
                1421-9670
                2001
                October 2001
                19 October 2001
                : 21
                : 5
                : 368-372
                Affiliations
                Department and Clinic of Internal Medicine and Diabetology, Silesian School of Medicine, Zabrze, Poland
                Article
                46276 Am J Nephrol 2001;21:368–372
                10.1159/000046276
                11684796
                731aeadd-999a-4d75-badc-a7bc614e0a58
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Tables: 2, References: 21, Pages: 5
                Categories
                Clinical Study

                Cardiovascular Medicine,Nephrology
                End-stage renal disease,G-protein β3 subunit,Gene polymorphism,Transmission/disequilibrium test

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