Stroke patients with
poor outcomes with
arginine variant of p53
with poor outcomes
with arginine variant
Gene variant ups
damage in brain
More cell suicide linked to
poorer recovery after stroke
p53 had previously been shown to help
protect against cancer by increasing
apoptosis, a cell suicide program that
gets rid of damaged cells. Brain cells can
also undergo apoptosis after a stroke,
but in the brain it’s a bad thing, leading
to more widespread damage.
Angeles Almeida of the University
Hospital of Salamanca and colleagues
tested nerve cells that make either the
arginine or the proline version of p53 to
see how the variants acted in the brain.
“The difference was huge,” Almeida
says. Cells with the arginine version had
at least two times greater capacity to
undergo apoptosis than did cells with the
proline variant. And the molecular difference has consequences for the whole
brain; when researchers tested the DNA
of stroke and brain hemorrhage patients,
the team found that a patient’s p53 variant correlated with how well the person
had recovered after three months.
By Tina Hesman Saey
A naturally occurring genetic variant
may help predict who will do well after
a stroke and who won’t. People who have
two copies of a particular version of the
Tp53 gene have a poor prognosis after
stroke and brain hemorrhages, researchers in Spain report online February 28
in the Journal of Experimental Medicine.
The difference between the two versions of the gene amounts to one small
change: swapping proline for arginine as
the 72nd link in a chain of amino acids
that make up a protein called p53.
The arginine-containing variant of
Of stroke patients with a poor prognosis, about 81 percent carried two copies
of the arginine variant. In hemorrhage
patients, about 91.5 percent of those with
a poor outcome had only the arginine variant. None of the people with two copies
of the proline variant had bad outcomes.
Those with one copy of each variant
tended to have good prognoses. The
results, Almeida says, indicate that controlling apoptosis may aid brain recovery.
“Their epidemiological data is really
quite convincing,” says David Johnson of
the University of Texas M.D. Anderson
Cancer Center in Smithville.
But Maureen Murphy of the Fox Chase
Cancer Center in Philadelphia doubts
that the variant will be a useful predictor
of stroke outcome for all ethnic groups.
African-Americans tend to have the proline version of p53, she notes, but also
have high rates of stroke, often with very
March 26, 2011 | science news | 11