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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1100.)
© 2005 American Heart Association, Inc.

Editorials

Quest for Genes Regulating Plasma Fibrinogen Concentration

Still a Long Way to Go

Anders Hamsten; Maria Nastase Mannila; Angela Silveira

From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Correspondence to Professor Anders Hamsten, MD, PhD, FRCP, King Gustaf V Research Institute, Building M1, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden. E-mail anders.hamsten@medks.ki.se

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Identification of the genes and genetic variants that confer proneness to coronary heart disease (CHD) remains an outstanding challenge to the biomedical research community. A host of genes are likely to contribute, yet only a small fraction have so far been unequivocally identified. This is not least because of the limited increase in risk contributed by each susceptibility gene. Thus, in most instances, more than one gene aberration will be required (heritability is polygenic), and clinical disease results from multifaceted interactions between susceptibility genes and environmental factors. Heritability is also heterogeneous; ie, different constellations of susceptibility genes are involved in different individuals. Adding to the complexity is epistasis or gene–gene interactions, where interactions among loci result in the genetic effects at one locus differing in magnitude or direction as a consequence of the genotype at another locus.¹

See page 1287

One of the preferred molecular genetic approaches is to focus on the dissection of measurable quantitative traits that are associated with disease susceptibility in epidemiological studies. This is generally considered to be a more practicable strategy than to target affection status itself, the latter end point being even more complex, further distant from gene function, and statistically less informative. One example of an intermediate trait that translates variation at the gene level into variation in the risk of CHD is the measure of plasma fibrinogen concentration. The plasma fibrinogen concentration is an established risk factor for CHD,² and several pathophysiological mechanisms have been identified, linking plasma fibrinogen to the development . . . [Full Text of this Article]

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A Genome Search for Genetic Determinants That Influence Plasma Fibrinogen Levels

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Arterioscler Thromb Vasc Biol 2005 25: 1287-1292. [Abstract] [Full Text] [PDF]