The Assessment of Interleukin-18 on the Risk of Coronary Heart Disease

Weiju       Sun; Ying       Han; Shuo       Yang; He       Zhuang; Jingwen       Zhang; Liang       Cheng; Lu       Fu

doi:10.2174/1573406415666191004115128

Abstract

Background: Observational studies support the inflammation hypothesis in coronary heart disease (CHD). As a pleiotropic proinflammatory cytokine, Interleukin-18 (IL-18), has also been found to be associated with the risk of CHD. However, to our knowledge, the method of Mendelian Randomization has not been used to explore the causal effect of IL-18 on CHD.

Objective: To assess the causal effect of IL-18 on the risk of CHD.

Methods and Results: Genetic variant instruments for IL-18 were obtained from information of the CHS and InCHIANTI cohort, and consisted of the per-allele difference in mean IL-18 for 16 independent variants that reached genome-wide significance. The per-allele difference in log-odds of CHD for each of these variants was estimated from CARDIoGRAMplusC4D, a two-stage meta -analysis. Two-sample Mendelian Randomization (MR) was then performed. Various MR analyses were used, including weighted inverse-variance, MR-Egger regression, robust regression, and penalized regression. The OR of elevated IL-18 associated with CHD was only 0.005 (95%CI -0.105~0.095; P-value=0.927). Similar results were obtained with the use of MR-Egger regression, suggesting that directional pleiotropy was unlikely biasing these results (intercept -0.050, P-value=0.220). Moreover, results from the robust regression and penalized regression analyses also revealed essentially similar findings.

Conclusion: Our findings indicate that, by itself, IL-18 is unlikely to represent even a modest causal factor for CHD risk.

Keywords: Interleukin-18, cytokines, coronary heart disease, risk, casual effect, Mendelian Randomisation.

« Previous Next »

Graphical Abstract

[1] 
Libby, P.; Ridker, P.M.; Hansson, G.K. Progress and challenges in translating the biology of atherosclerosis. Nature,  2011, 473,(7347), 317-325.
[http://dx.doi.org/10.1038/nature10146] [PMID: 21593864] 
[2] 
Hansson, G.K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med.,  2005, 352,(16), 1685-1695.
[http://dx.doi.org/10.1056/NEJMra043430] [PMID: 15843671] 
[3] 
Kaptoge, S.; Di Angelantonio, E.; Lowe, G.; Pepys, M.B.; Thompson, S.G.; Collins, R.; Danesh, J. Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet,  2010, 375,(9709), 132-140.
[http://dx.doi.org/10.1016/S0140-6736(09)61717-7] [PMID: 20031199] 
[4] 
Danesh, J.; Lewington, S.; Thompson, S.G.; Lowe, G.D.; Collins, R.; Kostis, J.B.; Wilson, A.C.; Folsom, A.R.; Wu, K.; Benderly, M.; Goldbourt, U.; Willeit, J.; Kiechl, S.; Yarnell, J.W.; Sweetnam, P.M.; Elwood, P.C.; Cushman, M.; Psaty, B.M.; Tracy, R.P.; Tybjaerg-Hansen, A.; Haverkate, F.; de Maat, M.P.; Fowkes, F.G.; Lee, A.J.; Smith, F.B.; Salomaa, V.; Harald, K.; Rasi, R.; Vahtera, E.; Jousilahti, P.; Pekkanen, J.; D’Agostino, R.; Kannel, W.B.; Wilson, P.W.; Tofler, G.; Arocha-Piñango, C.L.; Rodriguez-Larralde, A.; Nagy, E.; Mijares, M.; Espinosa, R.; Rodriquez-Roa, E.; Ryder, E.; Diez-Ewald, M.P.; Campos, G.; Fernandez, V.; Torres, E.; Marchioli, R.; Valagussa, F.; Rosengren, A.; Wilhelmsen, L.; Lappas, G.; Eriksson, H.; Cremer, P.; Nagel, D.; Curb, J.D.; Rodriguez, B.; Yano, K.; Salonen, J.T.; Nyyssönen, K.; Tuomainen, T.P.; Hedblad, B.; Lind, P.; Loewel, H.; Koenig, W.; Meade, T.W.; Cooper, J.A.; De Stavola, B.; Knottenbelt, C.; Miller, G.J.; Cooper, J.A.; Bauer, K.A.; Rosenberg, R.D.; Sato, S.; Kitamura, A.; Naito, Y.; Palosuo, T.; Ducimetiere, P.; Amouyel, P.; Arveiler, D.; Evans, A.E.; Ferrieres, J.; Juhan-Vague, I.; Bingham, A.; Schulte, H.; Assmann, G.; Cantin, B.; Lamarche, B.; Després, J.P.; Dagenais, G.R.; Tunstall-Pedoe, H.; Woodward, M.; Ben-Shlomo, Y.; Davey Smith, G.; Palmieri, V.; Yeh, J.L.; Rudnicka, A.; Ridker, P.; Rodeghiero, F.; Tosetto, A.; Shepherd, J.; Ford, I.; Robertson, M.; Brunner, E.; Shipley, M.; Feskens, E.J.; Kromhout, D.; Dickinson, A.; Ireland, B.; Juzwishin, K.; Kaptoge, S.; Lewington, S.; Memon, A.; Sarwar, N.; Walker, M.; Wheeler, J.; White, I.; Wood, A. Fibrinogen Studies Collaboration. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA,  2005, 294,(14), 1799-1809.
[PMID: 16219884] 
[5] 
Elliott, P.; Chambers, J.C.; Zhang, W.; Clarke, R.; Hopewell, J.C.; Peden, J.F.; Erdmann, J.; Braund, P.; Engert, J.C.; Bennett, D.; Coin, L.; Ashby, D.; Tzoulaki, I.; Brown, I.J.; Mt-Isa, S.; McCarthy, M.I.; Peltonen, L.; Freimer, N.B.; Farrall, M.; Ruokonen, A.; Hamsten, A.; Lim, N.; Froguel, P.; Waterworth, D.M.; Vollenweider, P.; Waeber, G.; Jarvelin, M.R.; Mooser, V.; Scott, J.; Hall, A.S.; Schunkert, H.; Anand, S.S.; Collins, R.; Samani, N.J.; Watkins, H.; Kooner, J.S. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA,  2009, 302,(1), 37-48.
[http://dx.doi.org/10.1001/jama.2009.954] [PMID: 19567438] 
[6] 
Holmes, M.V.; Dale, C.E.; Zuccolo, L.; Silverwood, R.J.; Guo, Y.; Ye, Z.; Prieto-Merino, D.; Dehghan, A.; Trompet, S.; Wong, A.; Cavadino, A.; Drogan, D.; Padmanabhan, S.; Li, S.; Yesupriya, A.; Leusink, M.; Sundstrom, J.; Hubacek, J.A.; Pikhart, H.; Swerdlow, D.I.; Panayiotou, A.G.; Borinskaya, S.A.; Finan, C.; Shah, S.; Kuchenbaecker, K.B.; Shah, T.; Engmann, J.; Folkersen, L.; Eriksson, P.; Ricceri, F.; Melander, O.; Sacerdote, C.; Gamble, D.M.; Rayaprolu, S.; Ross, O.A.; McLachlan, S.; Vikhireva, O.; Sluijs, I.; Scott, R.A.; Adamkova, V.; Flicker, L.; Bockxmeer, F.M.; Power, C.; Marques-Vidal, P.; Meade, T.; Marmot, M.G.; Ferro, J.M.; Paulos-Pinheiro, S.; Humphries, S.E.; Talmud, P.J.; Mateo Leach, I.; Verweij, N.; Linneberg, A.; Skaaby, T.; Doevendans, P.A.; Cramer, M.J.; van der Harst, P.; Klungel, O.H.; Dowling, N.F.; Dominiczak, A.F.; Kumari, M.; Nicolaides, A.N.; Weikert, C.; Boeing, H.; Ebrahim, S.; Gaunt, T.R.; Price, J.F.; Lannfelt, L.; Peasey, A.; Kubinova, R.; Pajak, A.; Malyutina, S.; Voevoda, M.I.; Tamosiunas, A.; Maitland-van der Zee, A.H.; Norman, P.E.; Hankey, G.J.; Bergmann, M.M.; Hofman, A.; Franco, O.H.; Cooper, J.; Palmen, J.; Spiering, W.; de Jong, P.A.; Kuh, D.; Hardy, R.; Uitterlinden, A.G.; Ikram, M.A.; Ford, I.; Hyppönen, E.; Almeida, O.P.; Wareham, N.J.; Khaw, K.T.; Hamsten, A.; Husemoen, L.L.; Tjønneland, A.; Tolstrup, J.S.; Rimm, E.; Beulens, J.W.; Verschuren, W.M.; Onland-Moret, N.C.; Hofker, M.H.; Wannamethee, S.G.; Whincup, P.H.; Morris, R.; Vicente, A.M.; Watkins, H.; Farrall, M.; Jukema, J.W.; Meschia, J.; Cupples, L.A.; Sharp, S.J.; Fornage, M.; Kooperberg, C.; LaCroix, A.Z.; Dai, J.Y.; Lanktree, M.B.; Siscovick, D.S.; Jorgenson, E.; Spring, B.; Coresh, J.; Li, Y.R.; Buxbaum, S.G.; Schreiner, P.J.; Ellison, R.C.; Tsai, M.Y.; Patel, S.R.; Redline, S.; Johnson, A.D.; Hoogeveen, R.C.; Hakonarson, H.; Rotter, J.I.; Boerwinkle, E.; de Bakker, P.I.; Kivimaki, M.; Asselbergs, F.W.; Sattar, N.; Lawlor, D.A.; Whittaker, J.; Davey Smith, G.; Mukamal, K.; Psaty, B.M.; Wilson, J.G.; Lange, L.A.; Hamidovic, A.; Hingorani, A.D.; Nordestgaard, B.G.; Bobak, M.; Leon, D.A.; Langenberg, C.; Palmer, T.M.; Reiner, A.P.; Keating, B.J.; Dudbridge, F.; Casas, J.P. InterAct Consortium. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ,  2014, 349,, g4164.
[http://dx.doi.org/10.1136/bmj.g4164] [PMID: 25011450] 
[7] 
Keavney, B.; Danesh, J.; Parish, S.; Palmer, A.; Clark, S.; Youngman, L.; Delépine, M.; Lathrop, M.; Peto, R.; Collins, R. Fibrinogen and coronary heart disease: test of causality by ‘Mendelian randomization’. Int. J. Epidemiol.,  2006, 35,(4), 935-943.
[http://dx.doi.org/10.1093/ije/dyl114] [PMID: 16870675] 
[8] 
Wei, L.; Zou, Q.; Liao, M.; Lu, H.; Zhao, Y. A novel machine learning method for cytokine-receptor interaction prediction. Comb. Chem. High Throughput Screen.,  2016, 19,(2), 144-152.
[http://dx.doi.org/10.2174/1386207319666151110122621] [PMID: 26552440] 
[9] 
Libby, P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr. Rev.,  2007, 65,(12 Pt 2), S140-S146.
[http://dx.doi.org/10.1301/nr.2007.dec.S140-S146] [PMID: 18240538] 
[10] 
Zeng, X.; Yuan, S.; Huang, X.; Zou, Q. Identification of cytokine via an improved genetic algorithm. Front. Comput. Sci.,  2015, 9,(4), 643-651.
[http://dx.doi.org/10.1007/s11704-014-4089-3] 
[11] 
Zou, Q.; Wang, Z.; Guan, X.; Liu, B.; Wu, Y.; Lin, Z. An approach for identifying cytokines based on a novel ensemble classifier. Biomed. Res. Int.,  2013, 2013, 686090
[http://dx.doi.org/10.1155/2013/686090] 
[12] 
Cheng, L.; Hu, Y. Human disease system biology. Curr. Gene Ther.,  2018, 18,(5), 255-256.
[http://dx.doi.org/10.2174/1566523218666181010101114] [PMID: 30306867] 
[13] 
Cheng, L.; Sun, J.; Xu, W.; Dong, L.; Hu, Y.; Zhou, M. OAHG: an integrated resource for annotating human genes with multi-level ontologies. Sci. Rep.,  2016, 6,, 34820.
[http://dx.doi.org/10.1038/srep34820] [PMID: 27703231] 
[14] 
Kaplanski, G. Interleukin-18: Biological properties and role in disease pathogenesis. Immunol. Rev.,  2018, 281,(1), 138-153.
[http://dx.doi.org/10.1111/imr.12616] [PMID: 29247988] 
[15] 
Mallat, Z.; Corbaz, A.; Scoazec, A.; Besnard, S.; Lesèche, G.; Chvatchko, Y.; Tedgui, A. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation,  2001, 104,(14), 1598-1603.
[http://dx.doi.org/10.1161/hc3901.096721] [PMID: 11581135] 
[16] 
Gerdes, N.; Sukhova, G.K.; Libby, P.; Reynolds, R.S.; Young, J.L.; Schönbeck, U. Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for atherogenesis. J. Exp. Med.,  2002, 195,(2), 245-257.
[http://dx.doi.org/10.1084/jem.20011022] [PMID: 11805151] 
[17] 
Blankenberg, S.; Tiret, L.; Bickel, C.; Peetz, D.; Cambien, F.; Meyer, J.; Rupprecht, H.J. AtheroGene Investigators. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation,  2002, 106,(1), 24-30.
[http://dx.doi.org/10.1161/01.CIR.0000020546.30940.92] [PMID: 12093765] 
[18] 
Blankenberg, S.; McQueen, M.J.; Smieja, M.; Pogue, J.; Balion, C.; Lonn, E.; Rupprecht, H.J.; Bickel, C.; Tiret, L.; Cambien, F.; Gerstein, H.; Münzel, T.; Yusuf, S. HOPE Study Investigators. Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation,  2006, 114,(3), 201-208.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.590927] [PMID: 16831981] 
[19] 
Tziakas, D.N.; Chalikias, G.K.; Kaski, J.C.; Kekes, A.; Hatzinikolaou, E.I.; Stakos, D.A.; Tentes, I.K.; Kortsaris, A.X.; Hatseras, D.I. Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach. Atherosclerosis,  2007, 193,(1), 196-203.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.06.016] [PMID: 16857204] 
[20] 
Blankenberg, S.; Luc, G.; Ducimetière, P.; Arveiler, D.; Ferrières, J.; Amouyel, P.; Evans, A.; Cambien, F.; Tiret, L. PRIME Study Group. Interleukin-18 and the risk of coronary heart disease in European men: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Circulation,  2003, 108,(20), 2453-2459.
[http://dx.doi.org/10.1161/01.CIR.0000099509.76044.A2] [PMID: 14581397] 
[21] 
Hung, J.; Knuiman, M.W.; Divitini, M.L.; Langton, P.E.; Chapman, C.L.; Beilby, J.P. C-reactive protein and interleukin-18 levels in relation to coronary heart disease: prospective cohort study from Busselton Western Australia. Heart Lung Circ.,  2008, 17,(2), 90-95.
[http://dx.doi.org/10.1016/j.hlc.2007.07.002] [PMID: 17851127] 
[22] 
Thompson, S.R.; Novick, D.; Stock, C.J.; Sanders, J.; Brull, D.; Cooper, J.; Woo, P.; Miller, G.; Rubinstein, M.; Humphries, S.E. Free Interleukin (IL)-18 levels, and the impact of IL18 and IL18BP genetic variation, in CHD patients and healthy men. Arterioscler. Thromb. Vasc. Biol.,  2007, 27,(12), 2743-2749.
[http://dx.doi.org/10.1161/ATVBAHA.107.149245] [PMID: 17951325] 
[23] 
Everett, B.M.; Bansal, S.; Rifai, N.; Buring, J.E.; Ridker, P.M. Interleukin-18 and the risk of future cardiovascular disease among initially healthy women. Atherosclerosis,  2009, 202,(1), 282-288.
[http://dx.doi.org/10.1016/j.atherosclerosis.2008.04.015] [PMID: 18514203] 
[24] 
Cheng, L.; Wang, P.; Tian, R.; Wang, S.; Guo, Q.; Luo, M.; Zhou, W.; Liu, G.; Jiang, H.; Jiang, Q. LncRNA2Target v2.0: a comprehensive database for target genes of lncRNAs in human and mouse. Nucleic Acids Res.,  2019, 47,(D1), D140-D144.
[http://dx.doi.org/10.1093/nar/gky1051] [PMID: 30380072] 
[25] 
Jefferis, B.J.; Papacosta, O.; Owen, C.G.; Wannamethee, S.G.; Humphries, S.E.; Woodward, M.; Lennon, L.T.; Thomson, A.; Welsh, P.; Rumley, A.; Lowe, G.D.; Whincup, P.H. Interleukin 18 and coronary heart disease: prospective study and systematic review. Atherosclerosis,  2011, 217,(1), 227-233.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.03.015] [PMID: 21481392] 
[26] 
Kalina, U.; Ballas, K.; Koyama, N.; Kauschat, D.; Miething, C.; Arnemann, J.; Martin, H.; Hoelzer, D.; Ottmann, O.G. Genomic organization and regulation of the human interleukin-18 gene. Scand. J. Immunol.,  2000, 52,(6), 525-530.
[http://dx.doi.org/10.1046/j.1365-3083.2000.00836.x] [PMID: 11119255] 
[27] 
Koch, W.; Wolferstetter, H.; Schatke, A.; Schömig, A.; Kastrati, A. Interleukin 18 gene variation and risk of acute myocardial infarction. Cytokine,  2011, 56,(3), 786-791.
[http://dx.doi.org/10.1016/j.cyto.2011.09.006] [PMID: 22015107] 
[28] 
Peng, J.; Wang, H.; Lu, J.; Hui, W.; Wang, Y.; Shang, X. Identifying term relations cross different gene ontology categories. BMC Bioinformatics,  2017, 18,(16)(Suppl. 16), 573.
[http://dx.doi.org/10.1186/s12859-017-1959-3] [PMID: 29297309] 
[29] 
Peng, J.; Hui, W.; Shang, X. Measuring phenotype-phenotype similarity through the interactome. BMC Bioinformatics,  2018, 19,(Suppl. 5), 114.
[http://dx.doi.org/10.1186/s12859-018-2102-9] [PMID: 29671400] 
[30] 
Bowden, J.; Davey Smith, G.; Haycock, P.C.; Burgess, S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol.,  2016, 40,(4), 304-314.
[http://dx.doi.org/10.1002/gepi.21965] [PMID: 27061298] 
[31] 
Li, P.; Guo, M.; Wang, C.; Liu, X.; Zou, Q. An overview of SNP interactions in genome-wide association studies. Brief. Funct. Genomics,  2015, 14,(2), 143-155.
[http://dx.doi.org/10.1093/bfgp/elu036] [PMID: 25241224] 
[32] 
Cheng, L.; Zhuang, H.; Yang, S.; Jiang, H.; Wang, S.; Zhang, J. Exposing the causal effect of c-reactive protein on the risk of type 2 diabetes mellitus: a mendelian randomization study. Front. Genet.,  2018, 9,, 657.
[http://dx.doi.org/10.3389/fgene.2018.00657] [PMID: 30619477] 
[33] 
Bennett, D.A.; Holmes, M.V. Mendelian randomisation in cardiovascular research: an introduction for clinicians. Heart,  2017, 103,(18), 1400-1407.
[http://dx.doi.org/10.1136/heartjnl-2016-310605] [PMID: 28596306] 
[34] 
Fried, L.P.; Borhani, N.O.; Enright, P.; Furberg, C.D.; Gardin, J.M.; Kronmal, R.A.; Kuller, L.H.; Manolio, T.A.; Mittelmark, M.B.; Newman, A. The Cardiovascular Health Study: design and rationale. Ann. Epidemiol.,  1991, 1(3), 263-276.
[http://dx.doi.org/10.1016/1047-2797(91)90005-W] [PMID: 1669507] 
[35] 
Ferrucci, L.; Bandinelli, S.; Benvenuti, E.; Di Iorio, A.; Macchi, C.; Harris, T.B.; Guralnik, J.M. Subsystems contributing to the decline in ability to walk: bridging the gap between epidemiology and geriatric practice in the InCHIANTI study. J. Am. Geriatr. Soc.,  2000, 48,(12), 1618-1625.
[http://dx.doi.org/10.1111/j.1532-5415.2000.tb03873.x] [PMID: 11129752] 
[36] 
Bowden, J.; Davey Smith, G.; Burgess, S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int. J. Epidemiol.,  2015, 44,(2), 512-525.
[http://dx.doi.org/10.1093/ije/dyv080] [PMID: 26050253] 
[37] 
Whitman, S.C.; Ravisankar, P.; Daugherty, A. Interleukin-18 enhances atherosclerosis in apolipoprotein E(-/-) mice through release of interferon-gamma. Circ. Res.,  2002, 90,(2), E34-E38.
[http://dx.doi.org/10.1161/hh0202.105292] [PMID: 11834721] 
[38] 
Woodward, M.; Welsh, P.; Rumley, A.; Tunstall-Pedoe, H.; Lowe, G.D. Do inflammatory biomarkers add to the discrimination of cardiovascular disease after allowing for social deprivation? Results from a 10-year cohort study in Glasgow, Scotland. Eur. Heart J.,  2010, 31,(21), 2669-2675.
[http://dx.doi.org/10.1093/eurheartj/ehp115] [PMID: 19363058] 
[39] 
He, M.; Cornelis, M.C.; Kraft, P.; van Dam, R.M.; Sun, Q.; Laurie, C.C.; Mirel, D.B.; Chasman, D.I.; Ridker, P.M.; Hunter, D.J.; Hu, F.B.; Qi, L. Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels. Arterioscler. Thromb. Vasc. Biol.,  2010, 30,(4), 885-890.
[http://dx.doi.org/10.1161/ATVBAHA.109.199422] [PMID: 20150558] 
[40] 
Melzer, D.; Perry, J.R.; Hernandez, D.; Corsi, A.M.; Stevens, K.; Rafferty, I.; Lauretani, F.; Murray, A.; Gibbs, J.R.; Paolisso, G.; Rafiq, S.; Simon-Sanchez, J.; Lango, H.; Scholz, S.; Weedon, M.N.; Arepalli, S.; Rice, N.; Washecka, N.; Hurst, A.; Britton, A.; Henley, W.; van de Leemput, J.; Li, R.; Newman, A.B.; Tranah, G.; Harris, T.; Panicker, V.; Dayan, C.; Bennett, A.; McCarthy, M.I.; Ruokonen, A.; Jarvelin, M.R.; Guralnik, J.; Bandinelli, S.; Frayling, T.M.; Singleton, A.; Ferrucci, L. A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet.,  2008, 4,(5) e1000072
[http://dx.doi.org/10.1371/journal.pgen.1000072] [PMID: 18464913] 
[41] 
Lamkanfi, M.; Dixit, V.M. Inflammasomes and their roles in health and disease. Annu. Rev. Cell Dev. Biol.,  2012, 28,, 137-161.
[http://dx.doi.org/10.1146/annurev-cellbio-101011-155745] [PMID: 22974247] 
[42] 
Broz, P.; von Moltke, J.; Jones, J.W.; Vance, R.E.; Monack, D.M. Differential requirement for Caspase-1 autoproteolysis in pathogen induced cell death and cytokine processing. Cell Host Microbe,  2010, 8(6), 471-483.
[http://dx.doi.org/10.1016/j.chom.2010.11.007] [PMID: 21147462] 
[43] 
Grisoni, M.L.; Proust, C.; Alanne, M.; Desuremain, M.; Salomaa, V.; Kuulasmaa, K.; Cambien, F.; Nicaud, V.; Wiklund, P.G.; Virtamo, J.; Kee, F.; Tiret, L.; Evans, A.; Tregouet, D.A. Lack of association between polymorphisms of the IL18R1 and IL18RAP genes and cardiovascular risk: the MORGAM Project. BMC Med. Genet.,  2009, 10,, 44.
[http://dx.doi.org/10.1186/1471-2350-10-44] [PMID: 19473509] 
[44] 
Hernesniemi, J.A.; Anttila, K.; Nieminen, T.; Kähönen, M.; Mononen, N.; Nikus, K.; Turjanmaa, V.; Viik, J.; Lehtinen, R.; Lehtimäki, T. IL-18 gene polymorphism, cardiovascular mortality and coronary artery disease. Eur. J. Clin. Invest.,  2010, 40,(11), 994-1001.
[http://dx.doi.org/10.1111/j.1365-2362.2010.02356.x] [PMID: 20735470] 
[45] 
Tiret, L.; Godefroy, T.; Lubos, E.; Nicaud, V.; Tregouet, D.A.; Barbaux, S.; Schnabel, R.; Bickel, C.; Espinola-Klein, C.; Poirier, O.; Perret, C.; Münzel, T.; Rupprecht, H.J.; Lackner, K.; Cambien, F.; Blankenberg, S. AtheroGene Investigators. Genetic analysis of the interleukin-18 system highlights the role of the interleukin-18 gene in cardiovascular disease. Circulation,  2005, 112,(5), 643-650.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.519702] [PMID: 16043644] 
[46] 
Grisoni, M.L.; Proust, C.; Alanne, M.; DeSuremain, M.; Salomaa, V.; Kuulasmaa, K.; Cambien, F.; Nicaud, V.; Stegmayr, B.; Virtamo, J.; Shields, D.; Kee, F.; Tiret, L.; Evans, A.; Tregouet, D.A. MORGAM Project. Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project. Eur. J. Hum. Genet.,  2008, 16,(12), 1512-1520.
[http://dx.doi.org/10.1038/ejhg.2008.127] [PMID: 18628791] 
[47] 
Hernesniemi, J.A.; Karhunen, P.J.; Oksala, N.; Kähönen, M.; Levula, M.; Rontu, R.; Ilveskoski, E.; Kajander, O.; Goebeler, S.; Viiri, L.E.; Hurme, M.; Lehtimäki, T. Interleukin 18 gene promoter polymorphism: a link between hypertension and pre-hospital sudden cardiac death: the Helsinki Sudden Death Study. Eur. Heart J.,  2009, 30,(23), 2939-2946.
[http://dx.doi.org/10.1093/eurheartj/ehp316] [PMID: 19687159] 
[48] 
Burgess, S.; Bowden, J.; Dudbridge, F.; Thompson, S. G. Robust instrumental variable methods using multiple candidate instruments with application to Mendelian randomization. arXiv preprint arXiv, 2016, 1606.03729.
[49] 
Yang, H.; Lv, H.; Ding, H.; Chen, W.; Lin, H. iRNA-2OM: A Sequence-Based Predictor for Identifying 2′-O-Methylation Sites in Homo sapiens. J. Comput. Biol.,  2018, 25(11), 1266-1277.
[http://dx.doi.org/10.1089/cmb.2018.0004] [PMID: 30113871] 
[50] 
Feng, C.Q.; Zhang, Z.Y.; Zhu, X.J.; Lin, Y.; Chen, W.; Tang, H.; Lin, H. iTerm-PseKNC: a sequence-based tool for predicting bacterial transcriptional terminators. Bioinformatics,  2019, 35(9), 1469-1477.
[PMID: 30247625] 
[51] 
Zhang, T.; Tan, P.; Wang, L.; Jin, N.; Li, Y.; Zhang, L.; Yang, H.; Hu, Z.; Zhang, L.; Hu, C.; Li, C.; Qian, K.; Zhang, C.; Huang, Y.; Li, K.; Lin, H.; Wang, D. RNALocate: a resource for RNA subcellular localizations. Nucleic Acids Res.,  2017, 45(D1), D135-D138.
[PMID: 27543076] 
[52] 
Liang, Z.Y.; Lai, H.Y.; Yang, H.; Zhang, C.J.; Yang, H.; Wei, H.H.; Chen, X.X.; Zhao, Y.W.; Su, Z.D.; Li, W.C.; Deng, E.Z.; Tang, H.; Chen, W.; Lin, H. Pro54DB: a database for experimentally verified sigma-54 promoters. Bioinformatics,  2017, 33(3), 467-469.
[PMID: 28171531] 
[53] 
Cheng, L.; Yang, H.; Zhao, H.; Pei, X.; Shi, H.; Sun, J.; Zhang, Y.; Wang, Z.; Zhou, M. MetSigDis: a manually curated resource for the metabolic signatures of diseases. Brief. Bioinform.,  2019, 20(1), 203-209.
[http://dx.doi.org/10.1093/bib/bbx103] [PMID: 28968812] 
[54] 
Cheng, L.; Hu, Y.; Sun, J.; Zhou, M.; Jiang, Q. DincRNA: a comprehensive web-based bioinformatics toolkit for exploring disease associations and ncRNA function. Bioinformatics,  2018, 34(11), 1953-1956.
[http://dx.doi.org/10.1093/bioinformatics/bty002] [PMID: 29365045] 

Rights & Permissions Print Cite

Article Metrics

17

1

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1573406415666191004115128	Print ISSN 1573-4064
Publisher Name Bentham Science Publisher	Online ISSN 1875-6638

Medicinal Chemistry

The Assessment of Interleukin-18 on the Risk of Coronary Heart Disease

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Related Articles

Abstract