Toll-like receptor 4 gene (Asp299Gly) polymorphism associates with carotid artery elasticity. The cardiovascular risk in young Finns study.
OBJECTIVE
Early subclinical markers of atherosclerosis, such as carotid artery intima media thickness (IMT) and elasticity predict future coronary events. The G allele of the Toll-like receptor 4 (TLR-4) gene Asp299Gly polymorphism has been previously associated with decreased development of atherosclerosis and with lower risk of myocardial infractions. We wanted to examine the association of this polymorphism with carotid IMT and compliance in a population of young Finnish Caucasian adults.


METHODS
Carotid artery IMT and elasticity indices of 2201 study subjects who participated in a randomized multicenter study (cardiovascular risk in young Finns study) were measured with ultrasound. The genotyping was performed using the TaqMan 5'-nuclease assay.


RESULTS
According to multivariate linear regression analysis adjusted with potential confounders, the G allele carriers had significantly higher carotid arterial compliance, measured in increase of luminal diameter percentage in response to blood pressure rise of 10 mmHg, than did the AA homozygotes (beta=0.099 with 95% CI 0.029-0.169 and p=0.006). The difference between AA homozygotes and GG homozygotes was even more pronounced (beta=0.382 with 95% CI 0.119-0.644 and p=0.004). Variation in the TLR-4 genotype was not related with IMT. The results of the two independent study cohorts of Eastern and Western Finland were in accordance with the results of the whole combined study population.


CONCLUSIONS
The G allele of the TLR-4 gene Asp299Gly polymorphism is associated with increased carotid artery compliance in young adults. This beneficial effect of the G allele may reduce the risk of future cardiovascular events.
Hernesniemi
Jussi A
JA
Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Finland. jussi.hernesniemi@uta.fi
Raitakari
Olli T
OT
Kähönen
Mika
M
Juonala
Markus
M
Hutri-Kähönen
Nina
N
Marniemi
Jukka
J
Viikari
Jorma
J
Lehtimäki
Terho
T
D000328:Adult; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000502:physiology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D003187:Compliance; D004548:Elasticity; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014463:Ultrasonography
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4