GENE hunters looking for the causes of strokes and other common diseases may have been looking in the wrong place. It seems that common mutations in the DNA of mitochondria, tiny structures that form the energy powerhouses of cells, may protect people against strokes, and play a role in Parkinson鈥檚 and other complex diseases.
Until now mitochondrial DNA has only been associated with a few, rare disorders: catastrophic mutations can cause diseases such as MELAS, which results in muscle weakness and seizures. But recent studies have hinted that less problematic 鈥� but far more common 鈥� mitochondrial mutations might also be implicated in diseases with no obvious link to energy demand, including strokes.
Mitochondrial DNA varies from person to person, but humans can generally be divided into broad 鈥渉aplogroups鈥� on the basis of the combinations of mutations they possess. Patrick Chinnery at the University of Newcastle, UK, and his colleagues assigned haplogroups to 950 people who鈥檇 had strokes, 340 people with heart disease symptoms, and 2939 healthy volunteers, all of whom live in Oxfordshire, UK.
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They found that among those people who鈥檇 had strokes, half as many belonged to haplogroup 鈥淜鈥� as would be expected in the general population. The researchers conclude that K 鈥� which accounts for around 9 per cent of people of European ancestry 鈥� decreases the risk of stroke by 50 per cent compared with the other haplogroups. This makes it one of the best predictors of stroke risk identified so far 鈥� on a par with aggressively lowering blood pressure (The Lancet Neurology, .
Belonging to the other haplogroups did not alter the risk of stroke and haplogroup K鈥檚 protective effect didn鈥檛 extend to heart disease.
The result could help explain why genome-wide association studies 鈥� which only look at nuclear DNA 鈥� have so far failed to identify new genes associated with stroke, says Chinnery. 鈥淥ur findings indicate the importance of mitochondrial DNA as a genetic risk factor,鈥� he adds.
鈥淭his could explain why genome-wide association studies have failed to identify new stroke genes鈥�
It is not clear how mitochondrial mutations offer stroke protection but Chinnery speculates that those found in haplogroup K might produce fewer reactive oxygen species, which are known to contribute to the blood vessel damage that leads to strokes.
The next step is to examine whether different groups within haplogroup K are better protected against strokes than others, and to work out what the protective mechanism is.
Other recent studies suggest a link between specific mitochondrial haplogroups and other complex disorders, including diabetes, Parkinson鈥檚 and Alzheimer鈥檚, and the rate at which people with HIV develop AIDS. Some have even linked a haplogroup particularly prevalent among centenarians to longevity (PLoS One, ).
