TLR4 Asp299Gly polymorphism is not associated with coronary artery stenosis.
Inflammation and innate immunity may play a role in the pathogenesis of atherosclerosis. The Asp299Gly polymorphism in the toll-like receptor 4 (TLR4) gene reduces responsiveness to lipopolysaccharide and has been associated with reduced incidence and slower progression of carotid atherosclerosis. We analyzed this polymorphism in relation to susceptibility to and severity of coronary artery disease.


METHODS
1400 participants (mean age: 63 years, 31% female) in the Southampton Atherosclerosis Study were genotyped for the TLR4 Asp299Gly polymorphism using the tetra-primer PCR method.


RESULTS
There was no significant difference between the frequencies of the Asp/Gly or Gly/Gly genotypes combined, compared to the Asp/Asp genotype, in patients with 0, 1, 2 or 3 coronary arteries with >50% stenosis (chi2(3 d.f.)2=0.4, P=0.94). No associations were observed between genotype groups and cardiac risk factors (P>0.05).


CONCLUSIONS
The findings of this study do not support the hypothesis that the TLR4 Asp299Gly polymorphism influences predisposition to and progression of coronary artery disease.
Yang
Ian A
IA
Human Genetics Division (Mailpoint 808), University of Southampton School of Medicine, Tremona Road, Southampton SO16 6YD, UK. i.yang@soton.ac.uk
Holloway
John W
JW
Ye
Shu
S
D023921:Coronary Stenosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D013223:Statistics as Topic; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors