Osteoprotegerin system and coronary atherosclerotic heart disease:an update / 天津医药

Osteoprotegerin (OPG), as a member of the tumor necrosis factor (TNF) superfamily, is a soluble secretary glycoprotein, which is accompanied with NF-κB receptor activator (RANK), NF-κB receptor activator ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to form osteoprotegerin system. A large number of clinical and experimental studies have confirmed that osteoprotegerin system participates in physiological processes such as endothelial function, inflammatory reaction, oxidative stress and apoptosis, which is expected to be a biomarker for the occurrence, development, severity and long-term prognosis of coronary heart disease. In this paper, we summarized the biological effects and mechanism of the osteoprotegerin system in the occurrence and development of coronary heart disease and its future clinical application.

Relationship of interleukin-6-572C/G promoter polymorphism and serum levels to post-percutaneous coronary intervention restenosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been recently reported that inflammatory mechanisms play an important role in in-stent restenosis (ISR) processes. Inflammatory factors after percutaneous coronary intervention (PCI) for dynamic monitoring can probably predict ISR. Functional polymorphisms in the promoter region of genes coding for inflammatory factors might be important for determining the magnitude of the inflammatory response. Thus, in the present study, we aimed to investigate the serial changes in serum interleukin-6 (IL-6) levels before and after PCI and the relationship between the -572C/G polymorphism in the promoter region of the IL-6 gene and ISR. We also discussed genetic polymorphisms in the inflammatory response to PCI.</p><p><b>METHODS</b>A total of 437 patients who successfully underwent bare metal stent (BMS) implantation with a follow-up angiography were divided into an ISR group (n = 166) and a non-ISR (NISR) group (n = 271). The IL-6 gene promoter polymorphism at position -572 was determined by restricted fragment length polymorphism using the polymerase chain reaction (PCR-RFLP) method. The serum IL-6 levels before and one day, five days and 180 days after PCI were determined by the radioimmunoassay method.</p><p><b>RESULTS</b>ISR patients showed higher IL-6 serum levels than NISR patients before PCI ((324.42 ± 28.14) ng/L vs. (283.22 ± 47.30) ng/L, P < 0.001), and one day post-PCI IL-6 serum levels in the ISR group also showed a significantly higher level than in the NISR group (P < 0.001). Increased IL-6 after PCI persisted at a statistically significant level throughout the study in ISR patients, whereas IL-6 levels had normalized five days after the procedure in NISR patients. One day post-PCI serum IL-6 level was the most accurate marker for diagnosis of ISR, the area under the ROC curve being 0.927 (95%CI 0.878 - 0.977). The cut-off value for IL-6 to predict ISR was over 355.50 ng/L, with a sensitivity of 0.968 and a specificity of 0.865. There were no significant differences in frequencies of -572 genotype and allele between the two groups (P > 0.05). One day post-PCI IL-6 serum levels in patients with the G allele was significantly higher than in patients without the G allele ((366.99 ± 49.37) ng/L vs. (347.20 ± 55.30) ng/L, P < 0.05). In the ISR group, one day post-PCI serum levels of IL-6 in patients with the G allele was also significantly higher than that in patients without the G allele ((405.67 ± 26.56) ng/L vs. (375.69 ± 38.81) ng/L, P < 0.05). Multivariate Logistic regression analysis revealed positive correlations between male gender, one day post-PCI serum levels of IL-6, the pre-PCI degree of stenosis, the length of the target lesion stenosis, and restenosis; and there were negative correlations between the stent diameter, the diameter of the reference vessel before stent implantation and restenosis.</p><p><b>CONCLUSIONS</b>IL-6 is an early post-PCI inflammatory cytokine, and one day post-PCI serum IL-6 level is an independent risk factor for restenosis. The frequencies of IL-6 gene -572 genotype and allele are not different between patients with and without ISR in a Chinese Tianjin Han population, but carrying the IL-6 -572G allele is likely to increase an individual's susceptibility to ISR by promoting serum IL-6 levels.</p>

Relationship of interleukin-10 gene polymorphism with restenosis after percutaneous coronary intervention in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship of interleukin-10 gene (IL-10) polymorphism and the serum IL-10 level with restenosis after percutaneous coronary intervention (PCI) in Tianjin Chinese Han population and study the effect of IL-10 gene polymorphism on serum IL-10 level.</p><p><b>METHODS</b>Four hundred and thirty-seven patients who successfully underwent PCI with a follow-up angiography were divided into a restenosis group (n = 166) and non-restenosis group (n = 271). The IL-10 gene promoter polymorphism at position -592 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Meanwhile their serum IL-10 level before and 24 h after PCI was determined by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>(1) There was no significant difference in frequencies of -592 genotypes and alleles between the two groups (P > 0.05); (2) The 24 h post-PCI IL-10 serum level of restenosis group was significantly lower than that of the non-restenosis group [(82.67 ± 35.02) ng/L vs. (95.08 ± 32.26) ng/L, P < 0.05]; (3) The serum level of the A allele carriers (AA+AC) was significantly lower than that of the CC carriers [(86.13 ± 34.77) ng/L vs. (102.50 ± 27.52) ng/L, P < 0.05]; (4) In the restenosis group, the 24 h post-PCI serum level of IL-10 in the A allele carriers was also significantly lower than that in those without the A allele [(78.51 ± 34.09) ng/L vs. (102.19 ± 33.66) ng/L, P < 0.05]; (5) Logistic regression analysis revealed positive correlations between acute coronary syndrome patients, pre-PCI degree of stenosis, length of target stenosis lesion and restenosis (OR = 5.90, 1.86, 2.83 respectively); and there were negative correlations between 24 h post-PCI serum level of IL-10, the stent diameter, the diameter of reference vessel before stent implantation and restenosis(OR = 0.99, 0.70, 0.46 respectively).</p><p><b>CONCLUSION</b>(1) The IL-10 gene -592 C/A polymorphism was not associated with restenosis in the Tianjin Chinese Han population; (2) IL-10 is an early post-PCI inflammatory cytokine, 24 h post-PCI serum IL-10 level was an independent predictive factor for restenosis, the IL-10 A allele carriers may have increased incidence of in-stent restenosis (ISR) by reducing the serum IL-10 levels.</p>

Association of paraoxonase polymorphisms and serum homocysteine thiolactone complex with coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between paraoxonase (PON) polymorphisms and serum homocysteine thiolactone (HTL) and coronary heart diseases.</p><p><b>METHOD</b>In this prospective study, serum complex of HTL levels using ELISA, and the lever of serum Hcy using high pressure liquid chromatography (HPLC), determined the PON1/T(-107)C and PON2/C311S genotypes using PCR-restriction fragment length polymorphisms 203 were measured in patients with angiographic documented coronary heart disease (CAD) and 117 controls.</p><p><b>RESULTS</b>Serum levels of Hcy and the complex of HTL in CAD patients were significantly higher than that in controls (P < 0.05). No significant difference was found in frequencies of PON1/T(-107)C genotypes and alleles (P > 0.05) between CAD patient and controls. The PON2/C311S (SS) genotype was lower in CAD patients than that in controls (P < 0.05), while the frequency of allele was similar between the two groups (P > 0.05). The T allele of PON1/T(-107)C and S alleles of PON2/C311S polymorphism were associated with lower plasma Hcy and HTL complex [Hcy (11.83 +/- 4.76) micromol/L vs (15.32 +/- 10.32) micromol/L, P < 0.05; HTL complex (24.36 +/- 9.30) U/ml vs (32.05 +/- 10.44) U/ml, P < 0.05]. The genetype PON2 and allele C were higher in CAD patients with type 2 diabetes than that in CAD patients without type 2 diabetes and controls (P < 0.005).</p><p><b>CONCLUSIONS</b>The elevation of serum Hcy and the complex of HTL were associated with increased risk of coronary heart disease. The allele PON1/(-107)T and PON2/311S might be protective for the development of atherosclerosis.</p>

Association of matrix metalloproteinase-9 and platelet membrane glycoprotein VI polymorphisms with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate serum level and gene polymorphisms of matrix metalloproteinase 9 (MMP-9), and platelet glycoprotein VI (GPVI) in patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>In a prospective study of 179 patients with documented ACS and 164 controls, we measured baseline serum MMP-9 levels using ELISA and determined the MMP-9/C-1562T and MMP-9/G5564A genotypes using PCR-restriction fragment length polymorphism. Fib serum level was measured by Clauss assay. We also analyzed the Fib/Bbeta-148C/T and GPVI/T13254C polymorphisms.</p><p><b>RESULTS</b>Serum levels of MMP-9 and Fib in ACS patients were significantly higher than in controls (P < 0.001), and serum level of Fib in the acute myocardial infarction group was higher than in patients with unstable angina (P < 0.05). No significant difference between ACS patients and controls was found in frequencies of MMP-9/C-1562T, MMP-9/G5564A, Fib/Bbeta-148C/T, and GPVI/T13254C genotypes and alleles (P > 0.05). The T allele of the Fib/Bbeta-148T polymorphism was associated with increased plasma Fib level (P < 0.05). There was a strong positive correlation between serum level of MMP-9 and Fib (r = 0.289, P < 0.01).</p><p><b>CONCLUSION</b>Serum levels of MMP-9 and Fib were independent risk factors of ACS. There was an obvious relationship between the Bbeta-148C/T mutation and high Fib level. No significant difference between controls and ACS patients was found in the frequencies of MMP-9 C-1562T and G5564A, Fib Bbeta-148C/T and GPVI T13254C genotypes and alleles (P > 0.05).</p>

Association of 4G/5G polymorphism in PAI1 promoter with PAI1 level in deep vein thrombosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To reveal the association of 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor 1 gene (PAI1) with plasma PAI1 level in deep vein thrombosis (DVT) in Chinese Han ethnic group.</p><p><b>METHODS</b>One hundred and twenty Chinese DVT patients and 120 healthy controls were recruited. The PAI1 promoter 4G/5G polymorphism was detected using polymerase chain reaction (PCR). The antigen of tissue-type plasminogen activator (tPA) or PAI1 was quantified by a commercially available enzyme-linked immunosorbent assay (ELISA) in DVT cases and health controlsì respectively.</p><p><b>RESULTS</b>Neither in the distribution of PAI1 promoter 4G/5G polymorphism nor in the frequencies of 4G and 5G allele was there a difference between two groups. The levels of PAI1 antigen in the carriers of the 4G/4G genotype were significantly higher than those either in the 4G/5G genotype or in the 5G/5G genotype; In the 4G/5G genotype or in the 5G/5G genotype the TG levels are an independently determinant factor of PAI1 antigen levels.</p><p><b>CONCLUSION</b>There is a close relationship of the PAI1 4G/5G polymorphism to its plasma level in deep vein thrombosis in Chinese Han ethnic group, although lack of association between this genetic variation and risk of DVT suggest no major cause-effect pathogenic role of this polymorphism by itself.</p>