Volume 182 - Issue 4
Possible genetic predisposition to cardiac effects
Authors: Hari Manev and Radmila M Manev
Med J Aust 2005; 182 (4): 198. || doi: 10.5694/j.1326-5377.2005.tb06656.x
Published online: 21 February 2005
Published online: 21 February 2005
Hari Manev,* Radmila M Manev†
* Professor, † Assistant Professor of Clinical Psychiatry, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, Illinois, 60612, USA hmanevATpsych.uic.edu
To the Editor: In their editorial on the rofecoxib controversy, Langton et al point out that large-scale but inconclusive studies failed to recognise an increased risk of heart attack and stroke in patients treated with this cyclooxygenase 2 (COX-2) inhibitor.1 Might something still be learned from these studies? Both COX-2 and 5-lipoxygenase (5-LOX) use the same substrate (arachidonic acid) to produce prostaglandins and leukotrienes, respectively. Overactive 5-LOX increases the risk of heart attack and stroke,2,3 and may be involved in the comorbidity of these disorders with anxiety and depression.4 In contrast, COX-2 appears to be cardioprotective. 5
Genetic diversity is responsible for overactive 5-LOX in some individuals and increases their risk for cardiovascular pathology.2,3 It is likely that patients with these alleles might be more susceptible to cardiovascular pathology in the absence of COX-2 activity — that is, be at increased risk of rofecoxib-provoked myocardial infarction and stroke.
If possible, retrospective studies should be attempted to determine the genotype of subjects treated with rofecoxib for 5-LOX2 and 5-LOX-activating protein3 polymorphisms and to relate these findings to rates of myocardial infarction and stroke.
References
- Langton PE, Hankey GJ, Eikelboom JW. Cardiovascular safety of rofecoxib (Vioxx): lessons learned and unanswered questions [editorial]. Med J Aust 2004; 181: 524-525. Previously published online, 26 October 2004.
- Dwyer JH, Allayee H, Dwyer KM, et al. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med 2004; 350: 29-37. i1085685
- Helgadottir A, Manolescu A, Thorleifsson G, et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 2004; 36: 233-239. i1085687
- Manev R, Manev H. 5-Lipoxygenase as a putative link between cardiovascular and psychiatric disorders. Crit Rev Neurobiol 2004; 16: 177-182. i1085689
- FitzGerald GA. Coxibs and cardiovascular disease. N Engl J Med 2004; 351: 1709-1711. CBBFDJAJ