Promoter polymorphism of the gene for CD14 receptor is not associated with sub-clinical carotid atherosclerosis in a community population.
BACKGROUND
The monocyte receptor CD14 is an important mediator of the inflammatory response to bacterial endotoxin. Recently, a functional polymorphism in the promoter of the CD14 gene (CD14-260C>T) was found to be associated with coronary heart disease. We examined if this polymorphism was associated with sub-clinical carotid atherosclerosis in a community population.


METHODS
A randomly selected community population (557 men and 553 women; aged 27-77 years) underwent conventional risk factor assessment and ultrasound evaluation of the common carotid intima-medial wall thickness (IMT) and carotid plaque formation. CD14-260C>T genotypes were examined by restriction fragment length polymorphism analysis. Chlamydia pneumoniae-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibody titres were determined by micro-immunofluorescence.


RESULTS
The carrier frequency of the T allele and TT genotype was 0.48 and 0.22 respectively. Genotype frequencies met Hardy-Weinberg expectation. There was no significant association of -260C>T genotypes with traditional risk factors. On multivariate analysis, there was no independent association of genotypes with common carotid IMT in men and women or with prevalence of carotid plaque in women. Contrary to expectation, men who were TT homozygotes relative to CC wild-type had a lower adjusted risk of carotid plaque formation (odds ratio 0.34, 95% confidence interval 0.17-0.69; P=0.003). There was no evidence that smoking or C. pneumoniae infection modified the association of genotypes with carotid IMT or plaque formation.


CONCLUSIONS
The CD14-260C>T gene polymorphism was not associated with an increased risk of sub-clinical carotid atherosclerosis in a community population.
Sir Charles Gairdner Hospital Unit of the School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia. jhung@cyllene@uwa.edu.au
Joseph
J
Hung
Brendan M
BM
McQuillan
Caroline M L
CM
Chapman
Peter L
PL
Thompson
John P
JP
Beilby
D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D017539:Tunica Intima / Q000473:pathology; D014463:Ultrasonography
D018950:Lipopolysaccharide Receptors