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.
Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility.
Wang X, Ria M, Kelmenson PM, Eriksson P Higgins DC, Samnegård A, Petros C, Rollins J, Bennet AM, Wiman B, De Faire U, Wennberg C, Olsson PG, Ishii N, Sugamura K, Hamsten A, Forsman-Semb K, Lagercrantz J, Paigen B.
Nature Genetics Online, 6 mars 2005.