Promoter Polymorphism of Interleukin18 in Angiographically Proven Coronary Artery Disease
Department of Cardiology, Xiangfan Central Hospital, Xiangfan, Hubei, China. Angiology
(Impact Factor: 2.97).
04/2009; 60(2):180-185. DOI: 10.1177/0003319708319939
Interleukin 18 (IL-18) is a pro-atherogenic cytokine associated with the occurrence of various cardiac complications. The IL-18 gene has a functional -137 G/C polymorphism (rs187238) in the promoter region. Using the ligase detection reaction-polymerase chain reaction, we genotyped a cohort of patients in Chinese Han population in Xiangfan region. Case patients of coronary artery disease and control patients were identified by coronary angiography. The plasma IL-18 concentrations were measured by ELISA. A significant increase of G allele or GG-genotype was observed in 241 case patients compared to 145 control individuals (frequency of G allele = 0.90 vs 0.83, p=0.004; frequency of GG-genotype = 0.81 vs 0.68, p = 0.005). In case patients, G allele carriers in multi-vessel disease patients had a higher occurrence rate when compared to single-vessel disease patients, but no significant difference was detected (frequency of G allele = 0.92 vs 0.88, p=0.107; frequency of GG-genotype = 0.84 vs 0.75, p = 0.089). IL-18 protein concentration of the -137GG genotype was much higher than concentration of the CG and CC genotype (case patients: 229.1±131.5 vs 122.7±73.6 pg/ml, P < 0.001; control patients: 65.9±31.6 vs 42.4±19.5 pg/ml, P < 0.001). To conclude, IL-18 promoter -137G/C polymorphism influences IL-18 levels and the occurrence of coronary artery disease, suggesting that IL-18 is causally involved in the development of atherosclerosis.
Available from: PubMed Central
- "In patients experiencing IS, peripheral
blood levels of IL-18 have been found to be significantly higher compared to healthy
individuals (9,10). Specifically, an SNP in the IL-18 promoter (designated
-607C/A) has been associated with the development of cardiovascular disease (11,12),
which can include vascular endothelial damage and formation of atherosclerosis,
processes that can induce stroke. This polymorphism affects the expression and
activity of IL-18 (13-15), thereby offering a potential mechanistic basis leading to
increased susceptibility to cardiovascular disease. "
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ABSTRACT: Single nucleotide polymorphisms in the promoter region of interleukin-18 (IL-18), an inflammatory cytokine, have been linked to susceptibility to many diseases, including cancer and immune dysfunction. Here, we explored the potential association between the IL-18 -607C/A (rs1946518) promoter region polymorphism and susceptibility to ischemic stroke (IS). This locus was amplified from peripheral blood samples of 386 IS patients (cases) and 364 healthy individuals (controls) by the polymerase chain reaction with sequence-specific primers. Significant differences were observed by the χ2 test in the -607C/A (rs1946518) genotype and allele frequencies between cases and controls (P < 0.05). Furthermore, after excluding for age, gender, smoking status, and hypertension, logistic regression indicated that IS susceptibility of -607C carriers increased 1.6 times (OR = 1.601, 95%CI = 1.148-2.233, P = 0.006) compared to -607A carriers. Additionally, similar increases in IS risk were noted for male patients or patients less than 65 years old. In conclusion, IL-18 -607C/A (rs1946518) promoter polymorphism is associated with IS susceptibility, and the C allele may confer increased IS risk.
Available from: Brian WC Tse
- "Of interest also is the observation that neutralization of endogenous IL-18 allows tumors to grow more rapidly indicating that in this model IL-18 is important for tumor immune surveillance (Fig. 1 C). In line with this observation, single nucleotide polymorphisms (SNPs) within the human IL-18 gene that are associated with lower promoter activity and lower gene expression , may influence susceptibility to certain cancers including prostate cancer , nasopharyngeal cancer  and esophageal squamous cell carcinoma . Moreover, human prostate cancer cell lines and clinical PCa specimens are reported to express IL-18 receptor α  and IL-18 expression was associated with better patient outcome. "
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ABSTRACT: Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4+ and CD8+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1−/− mice or in mice depleted of CD4+ and/or CD8+ cells than in normal mice. The tumors in RAG1−/− mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.
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ABSTRACT: Transformer is one of the most important equipment in power system, diagnosis of abnormal power transformer is important for the reliability of the power system and detecting the operating status of transformer accurately in time is of vital importance. A combined artificial neural network and expert systems tool (ANNES) is developed for transformer fault diagnosis using dissolved gas-in-oil analysis (DGA), ANNEPS takes advantage of the inherent positive features of each method and offers a further refinement of present techniques. The knowledge base of its expert system (ES) is derived from IEEE and IEC DGA standards and expert experiences to include as many known diagnosis rules as possible. The topology and training data set of its ANN are carefully selected to extract known as well as unknown diagnosis correlations implicitly. The combination of the ANN and ES outputs has an optimization mechanism to ensure high diagnosis accuracy for all genera! fault types. ANNES is database enhanced to facilitate archive management of equipment conditions, trend analysis, and further revision of the diagnosis rules. Depending on the analysis results, maintenance engineers can arrange corresponding maintenance plan and different maintenance contents. This Paper also issues a new condition-based power device maintenance method integrated with management information system (MIS). Several test show this method is very reliable an practical and the system has better performance than ANN or ES used.
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