http://www.timesonline.co.uk/tol/news/uk/health/article5029679.ece
October 28, 2008
Imprint of famine seen in genes of Second World War babies 60 years on
Dutch Food distribution coupons dating from WWII
Mark Henderson Science Editor
Malnourishment in the womb causes genetic changes that can still be seen
when
people reach middle and old age, according to new research that shows how
strongly environmental influences can interact with the human genome to
shape
health.
A study of children born during the Dutch “Hunger Winter”, a famine that
struck at the end of the Second World War, has found that some still bear
its
lasting genetic legacy more than six decades on.
The results offer some of the best evidence yet for the im****tance of
epigenetics, a process by which environmental factors can change the way
genes are switched on and off in the body.
Epigenetics suggests that the genome can “remember” certain influences to
which it is exposed, particularly early in life, which cause modifications
to
DNA that in turn alter the way it operates. On occasion, these changes may
even be passed on from one generation to the next.
Such epigenetic effects are increasingly thought to play an im****tant part
in
the influence of DNA over health, allowing nurture to combine with nature
to
affect growth, development, metabolism and susceptibility to disease.
The Hunger Winter of 1944 to 1945, when parts of the Netherlands
experienced
a severe famine because of a German food blockade, has long intrigued
researchers in epigenetics, because it provided a natural experiment for
studying how difficult environmental conditions might affect children.
Previous research has found that children whose mothers became pregnant
during the famine were at high risk of a wide variety of health problems,
including diabetes, obesity and cardiovascular disease. They also went on
to
have children who were more likely than usual to be born underweight.
This observation has led many scientists to propose that epigenetic
effects
might be responsible. The hypothesis was that the experience of growing in
a
womb short of nutrients might have caused genes to be altered to sup****t a
thrifty metabolism.
Such a mechanism could have evolved because the uterine environment was
usually a good guide to the conditions that would prevail once a child was
born, so encouraging it to store energy and use it sparingly would have
had
survival advantages.
This has now found sup****t from the new study, led by Bastiaan Heijmans,
of
Leiden University in the Netherlands. Details are published in the journal
Proceedings of the National Academy of Sciences.
One of the main mechanisms of epigenetics is a process called methylation,
by
which chemical groups are added to DNA to alter its function. Dr
Heijmans’s
team examined this in people born during the Hunger Winter, and their
siblings born when there was no famine.
Even though these people are now in their sixties, the imprint of the
famine
can still be seen in their genomes, in the shape of methylation patterns
on a
gene called insulin-like growth factor 2 or IGF2.
People who were exposed to famine during the first 10 weeks after their
conception had much less methylation of the IGF2 gene than did their
siblings
of the same ***. No effect was seen, however, among those who were 10
weeks
away from birth when the famine began.
The results seem to indicate that early prenatal development has a strong
effect on epigenetics, and can reprogramme the genome in ways that last
throughout life. The scientists are now seeking to investigate whether
this
correlates with health effects.
Dr Heijmans said: “Our study provides the first evidence that transient
environmental conditions early in human gestation can be recorded as
persistent changes in epigenetic information.
“Understanding how epigenetic control depends on early exposure may shed
light on the link between development and health over the lifespan and
ultimately suggest new ways to prevent human disease.”
Copyright 2008 Times Newspapers Ltd.
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