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.
Ben Assayag
Einor
E
Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Shenhar-Tsarfaty
Shani
S
Bova
Irena
I
Berliner
Shlomo
S
Usher
Sali
S
Peretz
Hava
H
Shapira
Itzhak
I
Bornstein
Natan M
NM
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