Preferences help
enabled [disable] Abstract
Number of results
2006 | 1 | 3 | 237-249
Article title

Aspirin and statin medication decreases the risk of myocardial infarction associated with LTA and NFKBIL1 polymorphisms

Title variants
Languages of publication
Lymphotoxin-α (LTA) is a cytokine involved in inflammatory reactions. NFKBIL1 is a regulator of the NF-κB complex. The study investigated the associations of LTA 804 C>A and NFKBIL1-63 T>A polymorphisms with the use of statin and acetylsalicylic acid (ASA) treatment in relation to myocardial infarction (MI).The study population comprised of 600 Finnish individuals who underwent coronary angiography volunteering for the Angiography and Genes Study. Genotypes were detected by the TaqMan 5′ nuclease assay. We found a interaction between the LTA genotype (p=0.002) and the NFKBIL1 genotype (p=0.012) and statin treatment in relation to MI. Subjects with the LTA AA or the NFKBIL1 AA genotype were at a 2.77 (95% CI:1.22-6.24) and 2.85 (95% CI:1.22-6.66) times higher risk, respectively, of suffering an MI when compared to other genotypes among statin non-users. ASA treatment also modulated associations between LTA and NFKBIL1 genotypes and MI (p=0.015 and p=0.028 respectively). The NFKBIL1-A-LTA-A haplotype showed a 61% increase in the risk of MI compared to the NFKBIL1-T-LTA-C haplotype among statin non-users.Anti-inflammatory medication modifies the genotype-related risk of MI, suggesting that subjects with LTA and NFKBIL1 AA haplotype might especially benefit from the treatment.
Physical description
1 - 9 - 2006
27 - 8 - 2006
  • [1] R. Ross: “Atherosclerosis-an inflammatory disease”, N. Engl. J. Med., Vol. 340(2), (1999), pp. 115–126.[Crossref]
  • [2] G. Stoll and M. Bendszus: “Inflammation and atherosclerosis: novel insights into plaque formation and destabilization”, Stroke, Vol. 37(7), (2006), pp. 1923–1932, Epub 2006 Jun 1.[Crossref]
  • [3] J.C. Padovani, A. Pazin-Filho, M.V. Simoes, J.A. Marin-Neto, M.A. Zago and R.F. Franco: “Gene polymorphisms in the TNF locus and the risk of myocardial infarction”, Thromb. Res., Vol. 100(4), (2000), pp. 263–269.[Crossref]
  • [4] T. Spies, G. Blanck, M. Bresnahan, J. Sands and J.L. Strominger: “A new cluster of genes within the human major histocompatibility complex”, Science, Vol. 243(4888), (1989), pp. 214–217.
  • [5] G. Messer, U. Spengler, M.C. Jung et al.: “Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production”, J. Exp. Med., Vol. 173(1), (1991), pp. 209–219.[Crossref]
  • [6] N.L. Paul: Ruddle NH. Lymphotoxin, Ann. Rev. Immunol., Vol. 6, (1988), pp. 407–438.[Crossref]
  • [7] K. Ozaki, Y. Ohnishi, A. Iida et al.: “Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction”, Nat. Genet., Vol. 32(4), (2002), pp. 650–654.[Crossref]
  • [8] M.R. Albertella and R.D. Campbell: “Characterization of a novel gene in the human major histocompatibility complex that encodes a potential new member of the I kappa B family of proteins”, Hum. Mol. Genet., Vol. 3(5), (1994), pp. 793–799. [Crossref]
  • [9] J.I. Semple, S.E. Brown, C.M. Sanderson and R.D. Campbell: “A distinct bipartite motif is required for the localization of inhibitory kappaB-like (IkappaBL) protein to nuclear speckles”, Biochem. J., Vol. 361(Pt 3), (2002), pp. 489–496.[Crossref]
  • [10] S. Ghosh, M.J. May and E.B. Kopp: “NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses”, Ann. Rev. Immunol., Vol. 16, (1998), pp. 225–260.[Crossref]
  • [11] F. Chen, V. Castranova, X. Shi and L.M. Demers: “New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases”, Clin. Chem., Vol. 45(1), (1999), pp. 7–17.
  • [12] W.T. Friedewald, R.I. Levy and D.S. Fredrickson: “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge”, Clin. Chem., Vol. 18(6), (1972), pp. 499–502.
  • [13] K.J. Livak: “Allelic discrimination using fluorogenic probes and the 5′ nuclease assay”, Genet. Anal., Vol. 14(5-6), (1999), pp. 143–149. [Crossref]
  • [14] P. Palomaki, H. Miettinen, H. Mustaniemi et al.: “Diagnosis of acute myocardial infarction by MONICA and FINMONICA diagnostic criteria in comparison with hospital discharge diagnosis”, J. Clin. Epidemiol., Vol. 47(6), (1994), pp. 659–666.[Crossref]
  • [15] M.H. Shishehbor, M.L. Brennan, R.J. Aviles et al.: “Statins promote potent systemic antioxidant effects through specific inflammatory pathways”, Circulation, Vol. 108(4), (2003), pp. 426–31, Epub 2003 Jul 14.[Crossref]
  • [16] C.H. Hennekens: “Update on aspirin in the treatment and prevention of cardiovascular disease”, Am. J. Manag. Care., Vol. 8, Suppl. 22, (2002), S691–S700.
  • [17] P. Libby: “Inflammation in atherosclerosis”, Nature, Vol. 420(6917), (2002), pp. 868–874.[Crossref]
  • [18] P.T. Kovanen, M. Kaartinen and T. Paavonen: “Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction”, Circulation, Vol. 92(5), (1995), pp. 1084–1088. [Crossref]
  • [19] R.T. Lee and P. Libby: “The unstable atheroma”, Arterioscler Thromb. Vasc. Biol., Vol. 17(10), (1997), pp. 1859–1867. [Crossref]
  • [20] V. Kahlke, C. Schafmayer, B. Schniewind, D. Seegert, S. Schreiber and J. Schroder: “Are postoperative complications genetically determined by TNF-beta NcoI gene polymorphism?”, Surgery, Vol. 135(4), (2004), Vol. 365–373 discussion 374–375.
  • [21] S. Schroeder, N. Borger, H. Wrigge et al.: “A tumor necrosis factor gene polymorphism influences the inflammatory response after cardiac operation”, Ann. Thorac. Surg., Vol.75(2), (2003), pp. 534–537.[Crossref]
  • [22] J. Braun, W. Marz, B.R. Winkelmann, H. Donner, K. Henning Usadel and K. Badenhoop: “Tumour necrosis factor beta alleles and hyperinsulinaemia in coronary artery disease”, Eur. J. Clin. Invest., Vol. 28(7), (1998), pp. 538–542.[Crossref]
  • [23] “A trio family study showing association of the lymphotoxin-alpha N26 (804A) allele with coronary artery disease”, Eur. J. Hum. Genet., Vol. 12(9), (2004), pp. 770-774.
  • [24] T. Wang, X. Zhang and J.J. Li: “The role of NF-kappaB in the regulation of cell stress responses”, Int. Immunopharmacol., Vol. 2(11), (2002), pp. 1509–1520.[Crossref]
  • [25] T. Yamashita, K. Hamaguchi, Y. Kusuda, A. Kimura, T. Sakata and H. Yoshimatsu: “IKBL promoter polymorphism is strongly associated with resistance to type 1 diabetes in Japanese”, Tissue Antigens, Vol. 63(3), (2004), pp. 223–230.[Crossref]
  • [26] A. Yamada, S. Ichihara, Y. Murase et al.: “Lack of association of polymorphisms of the lymphotoxin alpha gene with myocardial infarction in Japanese”, J. Mol. Med., Vol. 82(7), (2004), pp. 477–483, Epub 2004 Jun 3.[Crossref]
  • [27] R.S. Rosenson: “Pluripotential mechanisms of cardioprotection with HMG-CoA reductase inhibitor therapy”, Am. J. Cardiovasc. Drugs., Vol. 1(6), (2001), pp. 411–420.[Crossref]
  • [28] T. Miida, S. Hirayama and Y. Nakamura: “Cholesterol-independent Effects of Statins and New Therapeutic Targets: Ischemic Stroke and Dementia”, J. Atheroscler. Thromb., Vol. 11(5), (2004), pp. 253–264. [Crossref]
  • [29] M.S. Lauer: “Clinical practice. Aspirin for primary prevention of coronary events”, N Engl. J. Med., Vol. 346(19), (2002), pp. 1468–1474.[Crossref]
  • [30] “Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients”, BMJ., Vol. 324(7329), (2002), pp. 71-86.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.