A study of a closely knit family with several members suffering from a rare illness is providing what researchers say may be important clues to the cause of diseases ranging from high blood pressure to high cholesterol and even obesity and insulin resistance.
Starting with a woman suffering from low levels of magnesium in her blood, researchers found several family members with the same problem. They located a previously unknown genetic mutation that linked family members with several ailments in common, including high blood pressure and cholesterol levels.
The mutation affects the mitochondria, the power sources in each cell of the body. While this specific mutation may be rare, finding it is important because it alerts researchers that problems with the mitochondria may be linked to several ailments.
High blood pressure and cholesterol are very common problems, affecting a quarter of the adult population, and their cause has been unknown, Richard P. Lifton, lead researcher in the study, said in a telephone interview. His findings were published online Thursday by the journal Science.
Lifton, of the Howard Hughes Medical Institute, noted that high cholesterol and blood pressure often occur together, and the newly found mutation results in some people in this family with multiple illnesses, including those.
Since not everyone with hypertension or high cholesterol has the mutation, that raises the question of whether some other problem with the mitochondria, such as loss of function with aging, is also a factor in those diseases, he said.
“Epidemiological studies over the last twenty years have shown that hypertension, high cholesterol, high triglycerides, low magnesium, diabetes, insulin resistance and obesity tend to cluster with one another, but not in a simple way,” said Lifton, who works at Yale University.
“Not everybody who has any one of these traits has all of the others. The pattern of inheritance is complicated, and there hasn’t been a clear understanding of what’s driving this relationship,” he said.
Mitochondrial defects may link diseases
The new report may indicate that mitochondrial function is what ties these illnesses together.
Dr. Douglas S. Kerr said researchers have known that diabetes can be associated with mitochondrial defects in families, and this study brings together two other illnesses — high blood pressure and cholesterol — that, when combined with diabetes, are known as metabolic syndrome.
The finding “is a piece of the puzzle that points to a better understanding of the underlying mechanism. You have to collect many pieces of the puzzle, but this is an important one,” said Kerr, director of the Center for Inherited Disorders of Energy Metabolism at Case Western Reserve University in Cleveland.
The next goal, said Lifton, is to discover how mitochondrial defects cause illnesses.
It could be loss of energy, he said, since the mitochondria produce the body’s energy, or, with age, the mitochondria may stop working properly and begin producing toxins.
David Samuels, a professor at the Virginia Bioinformatics Institute at Virginia Tech, said that while the newly found mutation may be rare, “Our experience has been that if one mitochondrial mutation causes a disease, then other (mitochondrial DNA) mutations may also cause the same disease ... This gives us reason to look for these metabolic diseases in families with other mtDNA mutations,” said Samuels, who was not part of the research team.
“Other things can cause these diseases as well, but this mitochondrial DNA mutation is definitely one cause,” he said.
New targets for treatment
Philip A. Wood, director of the genomics division at the University of Alabama at Birmingham, said that while “this particular mitochondrial DNA mutation is likely rare and possibly limited to this large family, what it reveals is important.”
“That is, this is a new mechanism involving mitochondrial dysfunction that may help explain parts of disease processes that affect a large number of people, but due to different underlying causes of mitochondrial dysfunction such as aging,” Wood said.
He added that “rare genetic variants, like this one, reveal new targets not only for new drug development, but also may provide new approaches for diagnosis using an underlying cause, in this case a mitochondrial DNA mutation.”
The research was funded by the National Institutes of Health, the Howard Hughes Medical Institute and the American Heart Association.