Association of the -757T>C polymorphism in the CRP gene with circulating C-reactive protein levels and carotid atherosclerosis.
BACKGROUND
C-reactive protein (CRP) is an inflammatory protein that may play a role in the pathogenesis of atherosclerosis. CRP gene single nucleotide polymorphisms (SNPs) have been shown to be associated with CRP concentration; however, their independent effect on atherosclerosis has not been yet established. We aimed to determine whether the 5'-flanking -757T>C CRP gene polymorphism is associated with CRP concentration and carotid atherosclerosis.


METHODS
We genotyped the -757T>C CRP gene SNP and determined the concentration of serum CRP, the intima-media thickness (IMT) of the common carotid artery and the existence of plaque/s in 612 apparently healthy men and women aged 66+/-10 years.


RESULTS
Carriers of the CRP -757C allele presented with higher IMT and higher CRP concentrations (p=0.002, p=0.042, respectively). After adjustment for vascular risk factors, linear regression analysis showed an independent effect of CRP -757C allele on carotid IMT, beyond serum CRP concentrations. This SNP was also associated with carotid plaque occurrence (O.R. 1.74, 95% CI 1.1-2.77, p=0.002).


CONCLUSIONS
The present study provides evidence that a genetic variant of CRP gene is associated with carotid atherosclerosis, independently of traditional vascular risk factors. Further large-scale genomic studies are required, which may identify the genetic vulnerable subjects to develop atherosclerosis.
Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Einor
E
Ben Assayag
Shani
S
Shenhar-Tsarfaty
Irena
I
Bova
Shlomo
S
Berliner
Sali
S
Usher
Hava
H
Peretz
Itzhak
I
Shapira
Natan M
NM
Bornstein
D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors; D017539:Tunica Intima
D002097:C-Reactive Protein