Influence of the CD14 C260T promoter polymorphism on C-reactive protein levels in patients with coronary artery disease.
The CD14 receptor is an important mediator of inflammatory reactions, and its expression is under genetic control. The allelic variant of the C260T polymorphism located in the promoter region of the CD14 gene is associated with receptor expression and ischemic risk. To date, most studies assessing the functional implications of the C260T polymorphism have been performed under proinflammatory conditions (e.g., acute coronary syndromes), and whether gene sequence variations of the CD14 receptor have any functional effect on systemic inflammation in patients in a stable phase of their atherosclerotic disease process is unknown. Eighty-two patients with stable coronary artery disease were studied. High-sensitivity C-reactive protein (hs-CRP) was used as a measurement of systemic inflammation. The genotype distribution of the C260T polymorphism of the CD14 gene was as follows: CC in 18 of 82 patients (22%), TC in 48 of 82 patients (58.5%), and TT in 16 of 82 patients (19.5%). TT subjects had increased hs-CRP levels compared with carriers of the C allele (p = 0.04). A higher percentage of T allele homozygotes had hs-CRP levels >0.3 mg/dl (p = 0.01). Homozygosis status of the T allele was independently associated with hs-CRP levels >0.3 mg/dl (p = 0.004). In conclusion, these observations may support the findings in large-scale studies that T homozygotes of this functional polymorphism are at increased ischemic risk.
Bernardo
Esther
E
Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
Angiolillo
Dominick J
DJ
Ramírez
Celia
C
Cavallari
Ugo
U
Trabetti
Elisabetta
E
Sabaté
Manel
M
Hernández
Rosana
R
Moreno
Raul
R
Escaned
Javier
J
Alfonso
Fernando
F
Bañuelos
Camino
C
Costa
Marco A
MA
Bass
Theodore A
TA
Pignatti
Pier Franco
PF
Macaya
Carlos
C
Fernandez-Ortiz
Antonio
A
D000328:Adult; D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics*; D003596:Cytosine; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013941:Thymine
D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D003596:Cytosine; D002097:C-Reactive Protein; D013941:Thymine