on August 2, 2007
Published online before print August 2, 2007, doi: 10.1161/ATVBAHA.107.151530
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Submitted on May 11, 2007
Accepted on July 19, 2007
USF1 Contributes to High Serum Lipid Levels in Dutch FCHL Families and U.S. Whites With Coronary Artery Disease
Jenny C. Lee ;
From the Department of Human Genetics, David Geffen School of Medicine (J.C.L., D.W.-V., M.K., J.S.S, A.J., A.J.L., P.P), Departments of Biomathematics and Biostatistics (J.S.S.) and Departments of Medicine and Microbiology, Immunology, and Molecular Genetics (A.J.L.) at UCLA, Los Angeles, Calif; Department of Internal Medicine and the Cardiovascular Research Institute Maastricht (C.J.H.v.d.K., M.M.J.v.G., T.W.A.d.B.), Maastricht University, Maastricht, the Netherlands; Cleveland Clinic, Departments of Cardiovascular Medicine and Cell Biology, and Center for Cardiovascular Diagnostics & Prevention (M.B., S.L.H.), Cleveland, Ohio. Present address of T.W.A.d.B.: GlaxoSmithKline, Translational Medicine and Genetics, Research Triangle Park, NC.
* To whom correspondence should be addressed. E-mail: ppajukanta{at}mednet.ucla.edu.
Objective—Familial combined hyperlipidemia (FCHL) characterized by high serum total cholesterol or triglycerides (TGs) is a common dyslipidemia predisposing to coronary artery disease (CAD). Recently, the upstream transcription factor 1 (USF1) was linked and associated with FCHL and TGs in Finnish FCHL families. Here we examined the previously associated rs3737787 SNP in extended Dutch FCHL families (n=532) and in a cohort of US subjects who underwent diagnostic coronary angiography (n=1533).
Methods and Results—In males of the Dutch FCHL families, we observed significant sex-dependent associations between the common allele of rs3737787 and FCHL, TGs, and related metabolic traits (P=0.02 to 0.006). In the U.S. Whites, sex-dependent associations with TGs and related metabolic traits were observed for the common allele of rs3737787 in males (P=0.04 to 0.02) and rare allele in females (P=0.05 to 0.002). This intriguing relationship was further supported by the highly significant genotype x sex interactions observed for TGs in the Dutch and TGs and body mass index (BMI) in U.S. White subjects with CAD (P=0.0005 to 0.00004).
Conclusion—These data show that USF1 influences several cardiovascular risk factors in a sex-dependent manner in Dutch FCHL families and U.S. Whites with CAD. A significant interaction between sex and genotype was shown to affect TGs and BMI.
Key words: upstream transcription factor 1 • familial combined hyperlipidemia • coronary artery disease • association • lipids
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