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Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2222-7. Epub 2007 Aug 2.

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

Author information

1
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

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.

PMID:
17673701
DOI:
10.1161/ATVBAHA.107.151530
[Indexed for MEDLINE]

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