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Finnish families guide to gene behind abnormal lipid levels and atherosclerosis


Coronary heart disease is the leading cause of death in Western societies. Unfavorable serum lipid levels, high cholesterol, high triglycerides and low high-density lipoprotein (HDL) cholesterol, are well-known risk factors for atherosclerosis and coronary heart disease. Familial combined hyperlipidemia (FCHL), characterized by these changes in patients serum is the most common familial lipid disorder predisposing to coronary heart disease. FCHL is observed in about 20% of coronary heart disease patients under 60 years and the prevalence being 1% to 2% of Western populations. FCHL is a multifactorial lipid disorder caused by several genes and environmental factors. However, its etiology has remained largely unknown, leaving a significant number of affected individuals without proper prevention and care exposed to coronary heart disease.

The Finnish U.S. research team earlier reported the location of the FCHL gene on chromosome 1q (Pajukanta et al. Nature Genetics 1998) and has now identified the first major gene for FCHL, the most common hyperlipidemia predisposing to coronary heart disease (Pajukanta, Nature Genetics 2004).

The hyperlipidemia gene encodes the upstream transcription factor 1 (USF1) that regulates several genes participating in glucose and lipid metabolism. Since the same chromosome 1q21 region has also been linked to type 2 diabetes mellitus (T2DM) in numerous studies, it raises the possibility that the USF1 gene may explain the molecular background of not only hyperlipidemias but also the metabolic syndrome and type 2 diabetes. The study was performed by research groups lead by Professors Leena Peltonen, Paivi Pajukanta, Christian Ehnholm, Marja-Riitta Taskinen and Markku Laakso in the National Public Health Institute of Finland, in the University of California, Los Angeles (UCLA), USA, and in the Universities of Helsinki and Kuopio, Finland.

The discovery of the genetic basis for FCHL and its component traits (high serum total cholesterol, triglycerides and low HDL), will help develop more accurate diagnostic and preventive tools as well as biology-based therapeutic strategies for this common lipid disorder predisposing to coronary heart disease and perhaps also to metabolic syndrome, a growing health problem in Western countries.

Reference: Pajukanta et al. Nature Genetics, April 2004

More information: Leena Peltonen. Tel: 358-9-4744-83939, email:

Minna Meriläinen | alfa
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