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

Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction
Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction
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.
1744-6872
15-21
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Yang, Ian A.
f55f0532-ce8f-424c-af64-f8052139f2f2
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Yang, Ian A.
f55f0532-ce8f-424c-af64-f8052139f2f2
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab

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

Record type: Article

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.

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Published date: 2005

Identifiers

Local EPrints ID: 27141
URI: http://eprints.soton.ac.uk/id/eprint/27141
ISSN: 1744-6872
PURE UUID: 09b3c7f7-9799-4f77-b715-538d3b795567
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 26 Apr 2006
Last modified: 27 Apr 2022 01:39

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Contributors

Author: Ian A. Yang
Author: Shu Ye

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