Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
9856980
TITLE
G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension.
ABSTRACT
-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.
DATE PUBLISHED
1998 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 1998/12/18
medline 1998/12/18 00:01
entrez 1998/12/18 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Benjafield AV Benjafield A V AV Hypertension Gene Laboratory, Department of Physiology and Institute for Biomedical Research, University of Sydney, Sydney, New South Wales, Australia.
Jeyasingam CL Jeyasingam C L CL
Nyholt DR Nyholt D R DR
Griffiths LR Griffiths L R LR
Morris BJ Morris B J BJ
INVESTIGATORS
JOURNAL
VOLUME: 32
ISSUE: 6
TITLE: Hypertension
ISOABBREVIATION: Hypertension
YEAR: 1998
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0194-911X
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Hypertension
COUNTRY: United States
ISSNLINKING: 0194-911X
NLMUNIQUEID: 7906255
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Age of Onset
Australia epidemiology
Female epidemiology
GTP-Binding Proteins genetics
Genotype genetics
Humans genetics
Hypertension genetics
Male genetics
Middle Aged genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 3.6.1.- GTP-Binding Proteins
OTHER ID's