BACKGROUND:  Familial combined hyperlipidemia (FCHL) is a common familial dyslipidemia, characterized by high serum cholesterol, high serum triglycerides, or both. The condition is observed in about 20% of coronary heart disease patients under 60 years. FCHL is caused by multiple genes and environmental factors as well as by their interactions. Individuals with this condition have an increased risk of cardiovascular disease.. The outcome of FCHL treatment is related to early diagnosis, as well as treatment and compliance with therapy. Because the genetic background of this common lipid disorder is largely unknown, a significant number of affected individuals are not receiving proper preventative care and are exposed to premature coronary heart disease. The discovery of the genetic basis for FCHL and its component traits will thus help develop more accurate diagnostic and preventive tools.

INNOVATION:  Researchers at UCLA have discovered an association between the USF1 gene on human chromosome 1q and FCHL. Several variants of the USF1 gene region were linked and associated with FCHL and high serum triglycerides in Finnish FCHL families, implying that allelic variants of this gene region are conferring the susceptibility to the FCHL disorder. The association evidence was strongest in males with high triglycerides. The newly identified single nucleotide polymorphism (SNP) is one of the DNA sequence variants contributing to the susceptibility to the FCHL disorder. The other FCHL susceptibility variants are still largely unknown.

POTENTIAL APPLICATIONS 

• Diagnostics: as an individual test or part of an array of metabolic disease markers
• Pharmacogenomics: to assess association with drug responses to improve FCHL treatment efficacy

ADVANTAGES: The identified DNA sequence variant can be easily screened, and this invention may help develop more accurate diagnostic and preventive tools.

DEVELOPMENT-TO-DATE:  The invention was made and tested using Finnish FCHL families. The sample consisted of 60 extended Finnish FCHL families in which the DNA was available from 721 individuals.

Related Papers (Selected) Pajukanta P, Lilja HE, Sinsheimer JS, Cantor RM, Lusis AJ, Gentile M, Duan XJ, Soro-Paavonen A, Naukkarinen J, Saarela J, Laakso M, Ehnholm C, Taskinen MR, Peltonen L. Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nature Genetics. 36(4):371-6 (2004). More...

Reference: UCLA Case No. 2004-420

Patent Application: WO 2005/077974