PMID- 10526907
OWN - NLM
STAT- MEDLINE
DCOM- 19991109
LR  - 20190822
IS  - 0263-6352 (Print)
IS  - 0263-6352 (Linking)
VI  - 17
IP  - 10
DP  - 1999 Oct
TI  - 825T allele of the G-protein beta3 subunit gene (GNB3) is associated with
      impaired left ventricular diastolic filling in essential hypertension.
PG  - 1457-62
AB  - OBJECTIVE: Recently, a novel C825T polymorphism in the gene (GNB3) encoding for
      the G-protein beta3 subunit was identified. The 825T allele is associated with
      the generation of a novel splice variant, enhanced intracellular signal
      transduction, and arterial hypertension. In this study, we investigated the
      impact of the 825T allele on left ventricular structure and function in mild to
      moderate essential hypertensive subjects. METHODS: In 34 white patients with
      established mild to moderate essential hypertension (World Health Organization
      stage I or II, mean age 52 +/- 9 years) genotype analysis of GNB3 C825T
      polymorphism, insertion/deletion polymorphism of the ACE gene and 1166 A/C
      polymorphism of the AT1 receptor gene was performed. In each patient, 24 h
      ambulatory blood pressure measurement (SpaceLabs 90207) and two-dimensional
      guided M-mode echocardiography combined with Doppler sonography were performed.
      RESULTS: In our homogenous study group, the GNB3 825T allele was not associated
      with casual and 24 h ambulatory blood pressure (CC versus TC/TT: 144 +/- 13/92
      +/- 8 versus 151 +/- 14/97 +/- 7 and 143 +/- 11/92 +/- 7 versus 150 +/- 16/ 96
      +/- 9 mmHg, respectively) or parameters of left ventricular structure (relative
      wall thickness: CC versus TC/TT, 0.48 +/- 0.1 versus 0.46 +/- 0.1; left
      ventricular mass: CC versus TC/TT, 281 +/- 65 versus 299 +/- 80 g). However,
      transmitral flow variables reflecting left ventricular diastolic filling were
      impaired in patients expressing the TC/TT genotype (ratio of peak late (A) to
      early (E) velocities: CC versus TC/TT, 0.95 +/- 0.24 versus 1.2 +/- 0.26, P<
      0.02; velocity time integrals A/E: CC versus TC/TT, 0.57 +/- 0.16 versus 0.76 +/-
      0.23, P< 0.01) while all co-variables such as age, body mass index, ambulatory
      blood pressure, heart rate and end-diastolic volume were similar between the two 
      groups. If patients were stratified according to the I/D polymorphism of the ACE 
      gene and the A1166C polymorphism of the AT1 receptor gene, no differences in
      blood pressure, left ventricular structure or systolic and diastolic function of 
      the left ventricle were found between different genotypes. CONCLUSION: The GNB3
      825T allele was associated with impaired left ventricular diastolic filling in
      hypertensive subjects in this study. Since alterations in left ventricular
      filling have been identified as an early marker of hypertensive heart disease,
      the GNB3 C825T polymorphism may influence cardiac adaptation to increased
      afterload.
FAU - Jacobi, J
AU  - Jacobi J
AD  - Department of Medicine/Nephrology, University of Erlangen-Nurnberg, Germany.
FAU - Hilgers, K F
AU  - Hilgers KF
FAU - Schlaich, M P
AU  - Schlaich MP
FAU - Siffert, W
AU  - Siffert W
FAU - Schmieder, R E
AU  - Schmieder RE
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Hypertens
JT  - Journal of hypertension
JID - 8306882
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Blood Pressure/genetics
MH  - Female
MH  - GTP-Binding Proteins/*genetics
MH  - Humans
MH  - Hypertension/*genetics/physiopathology
MH  - Male
MH  - Middle Aged
MH  - Ventricular Function, Left/*genetics
EDAT- 1999/10/20 00:00
MHDA- 1999/10/20 00:01
CRDT- 1999/10/20 00:00
PHST- 1999/10/20 00:00 [pubmed]
PHST- 1999/10/20 00:01 [medline]
PHST- 1999/10/20 00:00 [entrez]
AID - 10.1097/00004872-199917100-00014 [doi]
PST - ppublish
SO  - J Hypertens. 1999 Oct;17(10):1457-62. doi: 10.1097/00004872-199917100-00014.