Toll‐like receptor 4 polymorphism is associated with coronary stenosis but not with the occurrence of acute or old myocardial infarctions

Abstract

Objective. Atherosclerosis is considered to be a chronic inflammatory disease. Toll‐like receptor 4 (TLR‐4), a key mediator in activating inflammatory cascade, has an A‐to‐G functional polymorphism that changes aspartic acid to glycine at position 299. TLR‐4 is activated by, for example, lipopolysaccharides. The purpose of this study was to investigate the role of a common Asp299Gly polymorphism of the TLR‐4 gene in atherosclerosis. Material and methods. The study comprised autopsy material from 657 men (the Helsinki Sudden Death Study; mean age 53, range 33–70 years). Results. Fewer G‐allele carriers had 3‐vessel coronary artery disease compared with AA homozygotes (OR 0.32; 95 % CI, 0.12–0.88, p = 0.027), and they also had a lower mean value for maximal coronary stenosis (p = 0.019). TLR‐4 polymorphism was not significantly associated with the occurrence of acute or old myocardial infarction (MI). Conclusions. The G allele of the TLR‐4 gene, which is associated with a lower inflammation response, was associated with a lower risk of coronary stenosis but not with the occurrence of MI and hence is not a major factor in the development of coronary atherosclerosis.

• Atherosclerosis
• autopsy study
• coronary artery disease
• genetics
• immunity

Acknowledgements

We thank Marita Koli for skilful technical assistance and Markus Perola for his contribution to the work. The study was supported by grants from the Medical Research Fund of the Tampere University Hospital, the Yrjö Jahnsson Foundation, the Finnish Foundation of Alcohol Research, the Elli and Elvi Oksanen Fund of the Pirkanmaa Fund under the auspices of the Finnish Cultural Foundation, the Emil Aaltonen Foundation, the Finnish Academy (grant no. 104821), and the Finnish Foundation of Cardiovascular Research.