C-reactive protein gene C1444T polymorphism and risk of recurrent ischemic events in patients with symptomatic intracranial atherostenoses.
BACKGROUND
High levels of C-reactive protein (CRP) are associated with an increased risk of further ischemic events in patients with symptomatic intracranial atherosclerotic disease (ICAD). It remains unknown to which extent this increased risk might be genetically predetermined. We aimed to investigate the relationship between a common genetic polymorphism of the CRP gene and the risk of recurrent ischemic events in symptomatic ICAD patients.


METHODS
We studied 75 consecutive patients with a first-ever cerebral ischemic event attributable to symptomatic ICAD. Blood samples were drawn 3 months after the qualifying event. Genomic DNA was isolated and the C1444T single nucleotide polymorphism (SNP) of the CRP gene was determined. The blood concentration of CRP was also measured. Patients underwent long-term clinical follow-up to detect the occurrence of further major ischemic events.


RESULTS
During a median follow-up time of 23 months, 18 patients (24%) suffered a major ischemic event (10 ischemic strokes, 3 transient ischemic attacks and 5 myocardial infarctions). Raised CRP levels at baseline (p = 0.02) and the presence of the T allele within the CRP C1444T SNP were associated with a higher risk of recurrent ischemic events (p = 0.02). Kaplan-Meier and multivariable Cox regression analyses adjusted for age, sex, vascular risk factors and CRP level identified that the presence of the T allele in the studied polymorphism predicted the occurrence of further ischemic events (hazard ratio 3.6, 95% confidence interval 1.2-11.1; p = 0.025).


CONCLUSIONS
The presence of the T allele within the CRP gene C1444T polymorphism may be associated with a higher risk of further ischemic events in symptomatic ICAD patients.
Arenillas
Juan F
JF
Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Barcelona, Spain.
Massot
Andreu
A
Alvarez-Sabín
Jose
J
Fernandez-Cadenas
Israel
I
del Rio-Espinola
Albert
A
Chacon
Pilar
P
Quintana
Manuel
M
Molina
Carlos A
CA
Rovira
Alex
A
Montaner
Joan
J
D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000150:complications*; D002546:Ischemic Attack, Transient / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012008:Recurrence; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*
D002097:C-Reactive Protein