The results of the study is published this week on Nature Genetics Online.

Researchers at Karolinska Institutet, in collaboration with the Jackson Laboratory in the USA, AstraZeneca and a Japanese research group, have scrutinised an area on chromosome 1 that is of demonstrable importance to the development of arteriosclerosis. The TNFSF4 gene was identified as the one responsible, as mice with mutations in this gene displayed a lower degree of atherosclerosis, while mice with more active variants of the gene displayed the opposite.

Studies of two patient groups revealed that a certain variant of the human homologue of the gene was more common in people who had a history of cardiac infarction than those without.

This is an example of how an unbiased genetic strategy based on a mice model can teach us more about common human diseases, says researcher Jacob Lagercrantz of the Gustav V research institute, Karolinska Institutet.

The gene codes for a protein called OX40L, which is involved in the activation of immunological T cells. These cells, in turn, play an important role in the pathogenesis of atherosclerosis and of a number of chronic inflammatory diseases. The new finding will spur further research into the relationship between the protein and cardiac infarction. Hopefully it will offer a new therapeutic technique for the treatment of atherosclerosis and thus reduce the risk of cardiac infarction.

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Using computer modeling, they demonstrated how this disease provided the selection pressure that forced up the frequency of the mutation from 1 in 20,000 at the time of the Black Death to values today of 1 in 10.

Lethal, viral haemorrhagic fevers were recorded in the Nile valley from 1500 BC and were followed by the plagues of Mesopotamia (700-450BC), the plague of Athens (430BC), the plague of Justinian (AD541-700) and the plagues of the early Islamic empire (AD627-744). These continuing epidemics slowly raised the frequency from the original single mutation to about 1 in 20,000 in the 14th century simply by conferring protection from an otherwise certain death.

Professor Duncan added: Haemorrhagic plague did not disappear after the Great Plague of London in 1665-66 but continued in Sweden, Copenhagen, Russia, Poland and Hungary until 1800. This maintenance of haemorrhagic plague provided continuing selection pressure on the CCR5-?„32 mutation and explains why it occurs today at its highest frequency in Scandinavia and Russia.

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