USF1 contributes to high serum lipid levels in Dutch FCHL families and U.S. whites with coronary artery disease.

Abstract

OBJECTIVE:

Familial combined hyperlipidemia (FCHL) characterized by high serum total cholesterol and/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).

CONCLUSIONS:

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.

• Authors: Jenny C Lee, Daphna Weissglas-Volkov, Mira Kyttälä, Janet S Sinsheimer, Anne Jokiaho, Tjerk W A de Bruin, Aldons J Lusis, Marie-Luise Brennan, Marleen M J van Greevenbroek, Carla J H van der Kallen, Stanley L Hazen, Päivi Pajukanta
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 27 Issue 10 Pg. 2222-7 (Oct 2007) ISSN: 1524-4636 [Electronic] United States
• PMID: 17673701 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Triglycerides
• USF1 protein, human
• Upstream Stimulatory Factors

Topics

• Adult
• Aged
• Body Mass Index
• Cohort Studies
• Coronary Angiography
• Coronary Artery Disease (blood, diagnostic imaging, genetics, physiopathology)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Humans
• Hyperlipidemia, Familial Combined (blood, complications, genetics, physiopathology)
• Male
• Metabolic Syndrome (complications, genetics)
• Middle Aged
• Netherlands
• Phenotype
• Polymorphism, Single Nucleotide
• Risk Factors
• Severity of Illness Index
• Sex Distribution
• Sex Factors
• Triglycerides (blood)
• United States
• Upstream Stimulatory Factors (genetics, metabolism)
• White People (genetics)