Sausages and cigarettes may cause arteries to clog, but a gene carried
by 24 per cent of the population also shares some of the blame.
Too much cholesterol in the blood can line arteries with plaque, causing
atherosclerosis, or hardening of the arteries. Diet, exercise and smoking
influence the fate of cholesterol, but so do several genes. Last week, scientists
in Texas said they had cracked the code for one such gene, and their results
could help in predicting who is at risk.
The gene is one of several that produce apolipoproteins, components
of the lipoproteins that shuttle cholesterol through the bloodstream and
to the liver. Called APOe, the gene comes in several versions, or alleles.
The three most common are called E2, E3 and E4.
Everyone has two versions of the gene, one inherited from each parent.
Fifty-seven per cent of the population is E3/E3, 24 per cent is E3/E4, and
13 per cent is E2/E3; other combinations are rare.
James Hixson, a geneticist at the Southwest Foundation for Biomedical
Research in San Antonio, Texas, examined DNA from 683 men, aged between
15 and 34, who had died in accidents. He then compared the allele type with
maps of the walls of major arteries removed during autopsy.
Every subject had some plaque covering the interior walls of their abdominal
artery. But those with the genetic combination E3/E4 showed the most damage;
32 per cent of the artery was covered. Those with the combination E3/E3
were somewhat better off, with 29 per cent covered, while the E2/E3 group
had 23 per cent damage.
The differences may seem small, says Hixson, but they are statistically
significant considering how young the subjects were. ‘The differences in
damage are expected to widen over time,’ he says. The subjects with the
E2/E3 allele had almost 40 per cent less damage than the E3/E4 group, suggesting
that the E2 allele has a positive effect on clearing cholesterol from the
Other studies have linked the E4 allele to a higher risk of heart attack.
In addition, Hixson found that the E2 allele is associated with lower blood
levels of low-density lipoprotein, believed to be the more harmful form
of cholesterol. ‘All this is really consistent,’ Hixson says, ‘which is
why I’ve started thinking about genetic testing. I think in 10 years or
so it’s going to be part of predicting health.’
Screening young people for a genetic predisposition to atherosclerosis
would pinpoint those who especially need to watch their diet and behaviour,
says Virgil Brown of the American Heart Association. Some 20 genes have
already been implicated in the body’s cholesterol pathway, but Frederick
Cornhill of Ohio State University, says Hixson’s research is the first to
show that a single gene is probably as important as any of the traditional
behavioural causes of the disease.