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In January 1998 scientists from Essen reported about an exciting research result: They could identify a mutation in a so-called G protein in patients with high blood pressure (hypertension). Due to this gene alteration signal transduction in all cells of the human body is enhanced. Professor Winfried Siffert, head of a research group at the Department of Pharmacology of the University Hospital at Essen, now reports that the association between this gene alteration and hypertension has been con-firmed in large, independent studies.
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In collaboration with scientists from the University Hospital of Regensburg the genes of 608 men and women were analysed in a cross-sectional population sample. This approach offers the advantage of investigating a representative sample from the general population. In contrast, case- control studies in which normotensive and hypertensive individuals are "enriched" sometimes suffer from unrecognised selec-tion bias. This study confirmed that individuals with the so-called "TT genotype" have an approximately 1.8-fold increased risk to develop hypertension compared to individuals with the "normal CC genotype". Interestingly, these individuals also had a three-fold increased risk to require two or more different drugs for blood pressure normalisation. "This could be a hint", Siffert states "that this gene altera-tion predisposes for a form of hypertension which is difficult to control". The co-operating team from Regensburg made another important discovery: Carriers of the gene alteration had significantly reduced blood levels of the hormone renin. "This form of low-renin hypertension associated with the gene alteration could indicate that affected individuals tend to retain salt" Siffert states.
The finding of the research group from Essen has now also been confirmed by Australian scientists. These investigators examined 110 hypertensive patients with a strong family history of hypertension (two affected parents) and compared them with a control group of 189 normotensive individuals without a family history. They found a drastic enrichment of the mutation in these hypertensive patients with a strong genetic background of hypertension.
"The causative role of the mutation in the pathogenesis of high blood pressure can now be taken as proven" Siffert says. But he also points at the possibility that the mutation might exert its action in connection with an unhealthy diet. In fact, in a recent Japanese study no association between the gene and hypertension could be found. "One very interesting point in this publication from Japan resides in the fact", so Siffert, "that the individuals investigated were rather lean". The research group from Essen currently examines whether the gene alteration is associated with overweight and obesity. Thus, the gene alteration could primarily predispose for obesity which is one of the major risk factors for hypertension.
The importance of these findings was only recently underscored in a review article which appeared in "The New England Journal of Medicine".
Meanwhile requests for genetic testing are increasing. This test is predominantly suitable for younger individuals with a family history of hypertension. At present only individuals with a private health insurance are scanned. The costs are in the range of DM 300.
References:
H. Schunkert, H. W. Hense, A. Döring, G. A. J. Riegger and W. Siffert. Association between a polymorphism in the G protein beta3 subunit gene and lower renin and elevated diastolic blood pressure. Hypertension 32:510-513, 1998.
A. V. Benjafield, C. L. Jeyasingam, D. R. Nyholt, L. R. Griffiths and B. J. Morris. G-Protein beta3 Subunit Gene (GNB3) Variant in Causation of Essential Hyper-tension. Hypertension 32 (6):1094-1097, 1998.
N. Kato, T. Sugiyama, H. Morita, H. Kurihara, Y. Yamori and Y. Yazaki. G protein beta3 subunit variant and essential hypertension in japanese. Hypertension 32 (5):935-938, 1998.
T. Iiri, Z. Farfel and H. R. Bourne. G-protein diseases furnish a model for the turn-on switch. Nature 394 (6688):35-38, 1998.
Z. Farfel, H. R. Bourne, and T. Iiri. The expanding spectrum of G protein diseases. N.Engl.J.Med. 340 (13):1012-1020, 1999.
Contact:Professor . Dr. Winfried Siffert, phone ++49 (201) 723-34 70
e-mail: winfried.siffert@uni-essen.de
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Ernährung / Gesundheit / Pflege, Medizin
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