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

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). 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.