Familial combined hyperlipidemia: upstream transcription factor 1 and beyond.
OBJECTIVE
Familial combined hyperlipidemia is a common complex disease that accounts for up to 20% of premature coronary heart disease. The upstream transcription factor 1, located on 1q21, was recently shown to be linked and associated with familial combined hyperlipidemia in Finnish families. Upstream transcription factor 1 is the first gene identified by positional cloning for familial combined hyperlipidemia. Replication studies are critical to investigation of complex diseases because only they can verify the importance of the original findings. We review recent studies that examine the genetic contribution and functional consequence of upstream transcription factor 1 variants to familial combined hyperlipidemia and type 2 diabetes mellitus. Aiming beyond upstream transcription factor 1, we also evaluate novel strategies that have made it possible to globally examine the genome and the transcriptome.


RESULTS
Three independent studies support the role of upstream transcription factor 1 in familial combined hyperlipidemia. The results for type 2 diabetes mellitus and the metabolic syndrome have been less conclusive highlight novel strategies for gene identification in familial combined hyperlipidemia.


CONCLUSIONS
Currently, genetic and functional evidence is supportive of a role for upstream transcription factor 1 in the etiology of familial combined hyperlipidemia and its component traits, although the mechanism of causality still remains largely unknown.
Department of Human Genetics bDepartment of Medicine/Division of Cardiology, University of California Los Angeles, Los Angeles, California 90095, USA.
Jenny C
JC
Lee
Aldons J
AJ
Lusis
Päivi
P
Pajukanta
D000818:Animals; D023281:Genomics; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics* / Q000378:metabolism*; D051720:Upstream Stimulatory Factors / Q000235:genetics / Q000378:metabolism*
C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors