G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension

Benjafield, A. V., Jeyasingam, C. L., Nyholt, D. R., Griffiths, L. R., & Morris, B. J. (1998) G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension. Hypertension, 32(6), pp. 1094-1097.

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-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.

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ID Code: 92185
Item Type: Journal Article
Refereed: Yes
Additional Information: Benjafield, A V
Jeyasingam, C L
Nyholt, D R
Griffiths, L R
Morris, B J
Comparative Study
Research Support, Non-U.S. Gov't
Hypertension. 1998 Dec;32(6):1094-7.
Keywords: Age of Onset, Australia/epidemiology, Female, GTP-Binding Proteins/chemistry/*genetics, Genotype, Humans, Hypertension/epidemiology/*genetics, Male, Middle Aged
DOI: 10.1161/01.HYP.32.6.1094
ISSN: 0194-911X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 1998 American Heart Association, Inc.
Deposited On: 27 Jan 2016 04:58
Last Modified: 27 Jan 2016 04:58

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