Mothers can pass on high blood pressure to their children
(Vienna, 20 April 2011) A study published at the start of April in the top journal “Circulation Research” shows that high blood pressure can be passed on via the female family line. A mutation in the genome of the mitochondria has been identified as the cause. The researchers from MedUni Vienna who participated in this study clarified the molecular mechanism of the disease.
In this international research project scientists from the USA, China and Austria examined five generations of an extended Chinese family where high blood pressure was very common. The result showed that more than 50% of family members from the mother’s side suffered from high blood pressure but none of the father’s descendents did.
Gene mutations identified as cause
The genetic examination of the patients revealed a mutation in the genome of the mitochondria, the power plants of our cells. Unlike the chromosomal genetic material, they are passed on solely from the mother to the descendents. With the mutation in the mitochondrial genetic material the energy supply can be disrupted in the affected cells, and via a mechanism which it has not been possible to study so far this can lead to high blood pressure.
Lack of supply and damage to the cells
The researchers located the mutation in the gene for isoleucine transfer RNA (tRNAIle). This RNA plays a central role in the translation of mitochondrial DNA into proteins. When examining the patients affected by high blood pressure the researchers discovered that the quantity of tRNAIle in the cells affected by the mutation was reduced by around 50%.
The molecular cause of this was discovered by Andrea Fettermann from the working group of Walter Rossmanith at the Centre for Anatomy and Cell Biology at MedUni Vienna: the mutation impairs an essential step of the synthesis of the tRNAIle which is catalysed by the enzyme RNase P. This mitochondrial enzyme was also only recently discovered by the working group (Holzmann et al., 2008, Cell 135, 462).
As a consequence of the reduction of the tRNAIle, important mitochondrial components are produced less by the affected cells. In turn this leads to a decrease in cell respiration and therefore in energy supply. The mitochondria are also the place where free radicals emerge. These chemical compounds attack different cell components and damage them. The researchers discovered an increased quantity of these substances in the mutated cells of the high blood pressure patients, which might also be caused by the gene mutation.
Mitochondrial mutations as a cause of disease
Mutations in the mitochondrial DNA can lead to many different diseases. Although the muscles and nervous system are particularly often impaired, nearly every other organ system can also be affected. Says Walter Rossmanith: “A mitochondrial mutation as a cause of high blood pressure is probably a special case but it illustrates how incredibly broad the range of mitochondrial diseases is. Mutations in tRNAs are particularly common and to understand the mechanisms which can lead to such different symptoms is a major challenge for the future.”
Walter Rossmanith’s research on this theme is supported by the Austrian Science Fund (FWF).
Participating scientists from MedUni Vienna:
Ao. Univ. Prof. Mag. Dr. Walter Rossmanith, head of the working group
Graduate biologist Andrea Fettermann, doctoral student
Mag. Andreas Taschner, doctoral student
all at the Centre for Anatomy & Cell Biology of MedUni Vienna
Publication in „Circulation Research“:
» Maternally Inherited Essential Hypertension Is Associated With the Novel 4263A>G Mutation in the Mitochondrial tRNAIle Gene in a Large Han Chinese Family.
Wang, S., R. Li, A. Fettermann, Z. Li, Y. Qian, Y. Liu, X. Wang, A. Zhou, J. Q. Mo, L. Yang, P. Jiang, A. Taschner, W. Rossmanith, and M.-X. Guan (2011).
Circ. Res. 108, 862-70.
» MedUni Wien Artikel zu RNase P