Abstract
Background: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). Methods: DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA. Results: For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group (p = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10–0.62, p = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 μg/mL) were reduced when compared to reference value. Conclusions: The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals.
Highlights
Atherosclerosis, a partially heritable disorder [1], is a chronic inflammatory disease of the blood vessels and underlies the vast majority of cardiovascular disease
Toll-Like-Receptor 4 (TLR-4) Results The allele and genotype carrier frequencies for TLR-4-Asp299Gly and TLR-4-Thr399Ile functional polymorphisms are summarized in Tables 2 and 3
HWE for the TLR-4-Asp299Gly polymorphism frequency is accepted (p > 0.05) while it isnot accepted for the TRL-4-Thr399Ile frequency (p = 0.0021)
Summary
Atherosclerosis, a partially heritable disorder [1], is a chronic inflammatory disease of the blood vessels and underlies the vast majority of cardiovascular disease. Studies using TLR-4 knockout mice have revealed that this receptor mediates cellular responses to cell-wall components of Gram-negative bacteria [10,11]. Mutations in this gene have been associated with differences in LPS responsiveness. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). The functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals
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