USF1 contributes to high serum lipid levels in Dutch FCHL families and U.S. 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).


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.
Lee
Jenny C
JC
Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Weissglas-Volkov
Daphna
D
Kyttälä
Mira
M
Sinsheimer
Janet S
JS
Jokiaho
Anne
A
de Bruin
Tjerk W A
TW
Lusis
Aldons J
AJ
Brennan
Marie-Luise
ML
van Greevenbroek
Marleen M J
MM
van der Kallen
Carla J H
CJ
Hazen
Stanley L
SL
Pajukanta
Päivi
P
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000235:genetics; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index; D017678:Sex Distribution; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood*; D014481:United States; D051720:Upstream Stimulatory Factors / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics*
D014280:Triglycerides; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors