A prospective evaluation of the CD14 C(-260)T gene polymorphism and the risk of myocardial infarction

Zee, Robert Y.L.; Lindpaintner, Klaus; Struk, Berthold; Hennekens, Charles H.; Ridker, Paul M.

doi:10.1016/s0021-9150(00)00698-5

Cited by 55 publications

(38 citation statements)

References 11 publications

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“…28) In addition, Unckelbach, et al reported that the T/T genotype was associated with MI in a small subgroup of low-risk, nonsmoker, normotensive patients, although there was no significant correlation between the CD14 polymorphism and patients who survived from MI. 29) On the other hand, Zee, et al reported that there was no significant association between CD14 polymorphism and the risk of MI, 30) Which appears to be in conflict with the above-mentioned observations and our findings in this study. However, Zee, et al examined only male patients.…”

Section: Discussioncontrasting

confidence: 99%

Association Study of CD14 Polymorphism With Myocardial Infarction in a Japanese Population

et al. 2003

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SUMMARYThere have been many studies investigating the association between gene polymorphisms and coronary artery disease (CAD) including myocardial infarction (MI), and some studies have shown that certain gene polymorphisms are associated with CAD/MI. However, the results of the association have sometimes been controversial. The reason may be that the contribution of genetic risk factors to CAD/MI varies depending on the ethnic, environmental, and habitual backgrounds, and differs between males and females. In this study, we analyzed 17 polymorphisms in 12 candidate genes for MI in 136 patients and 200 to 235 controls, and found that there is a significant association of MI with the polymorphisms in the genes for E-selectin and CD14 receptor. To further explore the association, we investigated the C-260 T polymorphism in the promoter region of the CD14 gene in 502 MI patients and 527 control subjects. The genotype distributions of the CD14 polymorphism were as follows; patients; T/T 32.5%, C/T 48.2%, C/C 19.3%, and controls; T/T 25.4%, C/T 52.8%, C/C 21.8%. The frequencies of the T/T homozygotes were significantly higher in the patients (OR = 1.41, P = 0.013) than in the control group, confirming the association of CD14 polymorphism with MI in Japanese. Stratification analyses further demonstrated that the association was more prominent in females and in patients with a relatively low body mass index, suggesting that the contribution of the CD14-linked genetic risk to MI differs with respect to gender and habitual background. (Jpn Heart J 2003; 44: 613-622)

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Section: Discussioncontrasting

confidence: 99%

Association Study of CD14 Polymorphism With Myocardial Infarction in a Japanese Population

et al. 2003

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“…The distribution of CC genotype in Taiwan is significantly low as compared with those in Western countries. 9,15,16 The mean fluorescence intensity (MFI) of mCD14 on PBMC and plasma levels of sCD14 were measured in 84 healthy individuals (age 20-45 years; mean7s.d., 23.874.3 years; 44 females and 40 males). As shown in Figure 1, mCD14 in TT genotypes (mean: 1818) are significantly higher than those in CT (mean: 1517; P ¼ 0.044) and CC (mean: 1603; P ¼ 0.034) genotypes.…”

Section: Resultsmentioning

confidence: 99%

A CD14 promoter polymorphism is associated with CD14 expression and Chlamydia-stimulated TNFα production

Eng¹,

Wang²,

Chen³

et al. 2004

Genes Immun

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CD14, a pattern recognition receptor on monocyte and macrophage, plays a central role in innate immunity through recognition of bacterial lipopolysaccharide and initiation of inflammatory response. Recently, CD14/À260C4T promoter gene polymorphism has been found to be related to a risk of inflammatory diseases. Our results showed that the C allele frequency among Chinese in Taiwan was lower than those in Western countries. The membrane CD14 expression was significantly higher in TT as compared with CT and CC genotypes (P ¼ 0.034, 0.044, respectively). There was a higher level of soluble CD14 in TT and CT genotypes than in CC genotypes. In addition, TNFa production in whole blood was significantly higher in TT genotype than in CC genotype after stimulation by Chlamydiae. In conclusion, the single base pair polymorphism of CD14 promoter gene is associated with CD14 expression and Chlamydia-stimulated TNFa production, and may thus play some role in the chlamydia-induced inflammatory response.

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“…This lack of association is in accordance with the negative results of the prospective evaluation of the CD14 polymorphism on the risk of future MI in the Physicians' Health Study. 23 Given the potential interaction between TLR4 and CD14 in mediating signal transduction of innate immunity, we hypothesized that the CD14 polymorphism or plasma sCD14 concentrations might modify the relation between TLR4 polymorphism and the risk of coronary event. Since in the literature, the TLR4/Gly 299 allele is associated with a blunted response by monocytes to LPS 6 and the CD14/CC genotype is associated with a lower density of CD14 receptors on monocytes 17 and lower sCD14 plasma levels, 16,24 individuals who carry both genotypes should be less sensitive to LPS than others, and hence at lower risk of CHD.…”

Section: Discussionmentioning

confidence: 99%

“…17,19,20 Conversely, the CC genotype was associated with an increased incidence of incident coronary occlusion and increased carotid artery intimamedia thickness (IMT). 21,22 One prospective study 23 and three retrospective ones 18,24,25 did not find any association between the polymorphism and the risk of coronary events. No relationship was found between plasma concentrations of sCD14 and stable coronary artery disease or carotid IMT.…”

Section: Introductionmentioning

confidence: 94%

TLR4/Asp299Gly, CD14/C-260T, plasma levels of the soluble receptor CD14 and the risk of coronary heart disease: The PRIME Study

et al. 2004

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TLR4 and CD14 are two components of the LPS receptor complex, which are considered to play a key role in the pathogenesis of atherosclerosis. TLR4/Asp299Gly and CD14/C-260T polymorphisms are thought to modulate the activity of this complex. The aim of the study was to examine the association between the TLR4/Asp299Gly and CD14/C-260T polymorphisms, plasma levels of the soluble receptor CD14 (sCD14), and the incidence of coronary heart disease (CHD) in a prospective cohort (the PRIME Study) of 9758 healthy men aged 50-59 years recruited in France and Northern Ireland. A nested case -control design was used, comparing the 249 participants who developed a CHD event during the 5-year follow-up with 492 population-and age-matched control subjects. The two polymorphisms were genotyped and baseline plasma concentrations of sCD14 were measured. None of the two polymorphisms, or sCD14 levels, either considered alone or in combination, were associated with the risk of CHD. The CD14/C-260T allele was associated with increased plasma concentrations of soluble thrombomodulin and vascular cell adhesion molecule-1 and, to a lesser extent, sCD14. No relationship was observed between the TLR4 polymorphism and, any of the inflammatory and endothelial markers measured. The TLR4/Asp299Gly and CD14/C-260T polymorphisms and plasma sCD14 concentrations do not appear as significant predictors of the risk of CHD in healthy individuals.

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A prospective evaluation of the CD14 C(-260)T gene polymorphism and the risk of myocardial infarction

Cited by 55 publications

References 11 publications

Association Study of CD14 Polymorphism With Myocardial Infarction in a Japanese Population

Association Study of CD14 Polymorphism With Myocardial Infarction in a Japanese Population

A CD14 promoter polymorphism is associated with CD14 expression and Chlamydia-stimulated TNFα production

TLR4/Asp299Gly, CD14/C-260T, plasma levels of the soluble receptor CD14 and the risk of coronary heart disease: The PRIME Study

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