Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction

Holloway, John, Yang, Ian and Ye, Shu (2005) Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction. Pharmacogenetics and Genomics, 15 1: 15-21.

Author Holloway, John
Yang, Ian
Ye, Shu
Title Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction
Journal name Pharmacogenetics and Genomics   Check publisher's open access policy
ISSN 1744-6872
Publication date 2005-01
Sub-type Article (original research)
Volume 15
Issue 1
Start page 15
End page 21
Total pages 7
Place of publication London, United Kingdom
Publisher Lippincott Williams and Wilkins
Language eng
Subject 1102 Cardiovascular Medicine and Haematology
Abstract Variation in the gene encoding toll-like receptor 4 (TLR4), a transmembrane receptor that mediates inflammatory responses to bacterial endotoxin, has been associated with susceptibility to atherosclerosis and its complications, such as myocardial infarction (MI), the pathogenesis of which involves inflammation. A recent study has also indicated that TLR4 gene variation influences the effect of statin treatment on reducing atherosclerosis complications. We studied the TLR4 gene Asp299Gly polymorphism in relation to susceptibility to myocardial infarction in a cohort of patients with angiographically documented coronary artery disease, and performed a meta-analysis using data sets from three independent studies. The meta-analysis showed that overall, odds ratio (OR) for MI was 0.73 [95% confidence interval (CI) 0.55-0.96, P=0.024] in 299Gly carriers compared to non-carriers, and there was no evidence of heterogeneity among the sample sets (P=0.679). In our patient cohort, a significant association of 299Gly bearing genotypes with lower susceptibility to myocardial infarction was observed only in patients receiving statin treatment, with 299Gly carriers having an OR of 0.49 (95% CI 0.27-0.78, P=0.015) for MI compared to non-carriers. These results are consistent with the notion that variation in the TLR4 gene contributes to inter-individual variability in susceptibility to coronary ischaemic events, and that TLR4 genotype and statin treatment may have a synergistic effect.
Keyword Genetics
Myocardial infarction
Toll-like receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
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Created: Mon, 02 Mar 2009, 16:22:07 EST by Ms Sarada Rao on behalf of School of Medicine