Allelic variants of upstream transcription factor 1 associate with carotid artery intima-media thickness: the Cardiovascular Risk in Young Finns study.
BACKGROUND
Polymorphisms of the upstream transcription factor 1 (USF1) have been associated with familial combined hyperlipidemia and coronary heart disease. The impact of this gene on subclinical atherosclerosis is unknown. Associations of 3 allelic variants of the USF1 gene and their haplotypes with carotid artery intima - media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) were studied in a population of Finnish healthy young adults.


RESULTS
The study population comprised 2,281 individuals participating in the Cardiovascular Risk in Young Finns study. IMT, CAC and FMD values were measured by ultrasound examination. Genotypes were analysed using the 5' nuclease assay. A significant difference in IMT was found for usf1s1 (rs3737787) and usf1s8 (rs2516838) genotypes (p-values 0.046 and 0.021, respectively). Moreover, there was a significant difference between groups in haplotype 1 and haplotype 2 for IMT (p-values 0.011 and 0.028 respectively). In multivariate stepwise linear regression models adjusted by age, sex, body mass index, systolic and diastolic blood pressures, smoking, C-reactive protein, glucose, high- and low-density lipoprotein-cholesterols and triglycerides there were significant associations for the usf1s1 minor genotype AA to predict low IMT (p=0.038) and usf1s8 minor genotype GG to predict high IMT (p=0.003). There was also a significant association for haplotype 2 to predict low IMT in the otherwise similar multivariate model (p=0.006). No associations were found for polymorphisms and CAC, FMD or serum lipids.


CONCLUSIONS
The rs2516838 and rs3737787 polymorphisms of USF1 influence the carotid artery IMT, which is a new finding.
Collings
Auni
A
Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, PO Box 2000, 33521 Tampere, Finland. Auni.Collings@pshp.fi
Höyssä
Salla
S
Fan
Meng
M
Kähönen
Mika
M
Hutri-Kähönen
Nina
N
Marniemi
Jukka
J
Juonala
Markus
M
Viikari
Jorma S A
JS
Raitakari
Olli T
OT
Lehtimäki
Terho J
TJ
D000293:Adolescent; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography; D051720:Upstream Stimulatory Factors / Q000235:genetics*
C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors