Poultry farmer Clayton B doesn't normally concern himself
with which came first, the chicken or the egg. But since
being house-bound by a sudden stroke, he's been pondering
if the elevated homocysteine levels they found when he
was rushed to emergency had anything to do with the attack
— or was it just a by- product. It was the only thing
out of the ordinary that the docs could find with the
otherwise healthy 67-year-old. A report in the January
15 issue of The Lancet reveals that researchers
have been investigating a similar question. Many stroke
victims have elevated homocysteine levels, yet until this
latest report it remained a mystery whether the rise in
this amino acid or the stroke came first.
T
VS C VARIANTS
Homocysteine levels are controlled both by diet —
folic acid and vitamin B can lower levels — and
by genetics. Dr Aroon Hingorani and colleagues from
UK's University College of London took advantage of
the latter to help unravel the homocysteine-stroke conundrum.
It was previously found that people who inherit the
'TT' form of a gene called MTHFR have higher
levels of homocysteine in their blood than people with
the 'CC' variant. The researchers reasoned that if elevated
homocysteine levels are the cause of stroke, rather
than a consequence, folks with the TT variant would
be at greater risk. Further, "since this polymorphism
was randomly distributed, its association with stroke
should not be biased or confounded" by factors like
smoking or wealth, according to the authors.
CROSS
THEIR TTs
Searches of the MEDLINE and EMBASE databases through
to 2003 unearthed 111 studies involving a total of over
13,000 people that were either concerned with the link
between homocysteine and the MTHFR gene, or that
addressed the association between the polymorphism and
stroke risk.
The authors reported that those
folks with the TT MTHFR gene variant tended to
have more homocysteine in their blood and their risk
of stroke was higher.
Dr Hingorani cautions, however,
that "positive studies tend to be more likely to be
reported than negative ones." Statistical tests were
run in an attempt to get around this reporting bias.
They proved negative but have low power, states Dr Hingorani.
"The only way to get round [bias] is to do new, really
large, genetic studies. However, randomized control
trials of homocysteine lowering will likely give the
definitive answer we need."
CLOSER
TO AN ANSWER
Given these caveats, he points out that "what [the study]
does not do is provide any evidence that use of folic
acid or B vitamins is likely to be beneficial [or] provide
any justification for measuring homocysteine or MTHFR
genotype to predict stroke in an individual at this
stage because the effect sizes (even if causal) are
small."
Nonetheless, the data "are consistent
with a causal relationship between homocyteine concentration
and stroke." So the scale is tilting more towards homocysteine
being a risk factor rather than an inconsequential after
effect.
Lancet
Jan 15, 2005;365:224-32
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