Abstract
Arachidonate 12/15-lipoxygenase (12/15-LOX) is a member of the lipid peroxidizing enzyme family and plays a major role in atherosclerosis. The present study aimed to evaluate whether or not the ALOX15 gene polymorphism is involved in ischemic stroke in northern Chinese Han population. Participants in a case–control study included 396 patients (239 males, 157 females) with ischemic stroke and 360 healthy subjects (211 males, 149 females). The rs7217186 polymorphism of the ALOX15 gene was analyzed by polymerase chain reaction and restriction fragment length polymorphism, while the rs2619112 polymorphism of the ALOX15 gene was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The frequencies of the CC genotype and the C allele of rs7217186 were higher in participants with ischemic stroke than in the control group [P = 0.014 in males, P = 0.007 in atherosclerosis ischemic stroke (ACI)]. The frequencies of the AA genotype and the A allele of rs2619112 were higher in participants with ischemic stroke than in the control group (P = 0.011 in males, P = 0.015 in ACI). Multiple logistic regression analysis revealed the significance of rs7217186 and rs2619112 in males and in ACI after adjustment for confounding factors. The rs7217186 and rs2619112 polymorphisms of the ALOX15 gene were associated with ischemic stroke in males and in patients with ACI in northern Chinese Han population.
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References
Assimes TL et al (2008) A near null variant of 12/15-LOX encoded by a novel SNP in ALOX15 and the risk of coronary artery disease. Atherosclerosis 198(1):136–144
Bolick DT et al (2005) 12/15-Lipoxygenase regulates intercellular adhesion molecule-1 expression and monocyte adhesion to endothelium through activation of RhoA and nuclear factor-kappaB. Arterioscler Thromb Vasc Bio 25(11):2301–2307
Bonita R et al (2004) The global stroke initiative. Lancet Neurol 3(7):391–399
Brash AR (1999) Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem 274(34):23679–23682
Chisolm GM, Steinberg D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 28(12):1815–1826
Deliri H et al (2011) Increased 12/15-lipoxygenase enhances cell growth, fibronectin deposition, and neointimal formation in response to carotid injury. Arterioscler Thromb Vasc Biol 31(1):110–116
Deng S et al (2010) CYP4F2 gene V433M polymorphism is associated with ischemic stroke in the male Northern Chinese Han population. Prog Neuropsychopharmacol Biol Psychiatry 34(4):664–668
Dichgans M (2007) Genetics of ischaemic stroke. Lancet Neurol 6(2):149–161
Dobrian AD et al (2011) Functional and pathological roles of the 12- and 15-lipoxygenases. Prog Lipid Res 50(1):115–131
Domingues-Montanari S et al (2008) Genetics of stroke: a review of recent advances. Expert Rev Mol Diagn 8(4):495–513
Elkind MS (2010) Inflammatory mechanisms of stroke. Stroke 41(10 Suppl):S3–S8
Feigin VL (2005) Stroke epidemiology in the developing world. Lancet 365(9478):2160–2161
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352(16):1685–1695
Hassan A, Markus HS (2000) Genetics and ischaemic stroke. Brain 123(Pt 9):1784–1812
Hersberger M (2010) Potential role of the lipoxygenase-derived lipid mediators in atherosclerosis: leukotrienes, lipoxins and resolvins. Clin Chem Lab Med 48(8):1063–1073
Hersberger M et al (2009) No association of two functional polymorphisms in human ALOX15 with myocardial infarction. Atherosclerosis 205(1):192–196
Kuhn H et al (2002) Mammalian arachidonate 15-lipoxygenases structure, function, and biological implications. Prostaglandins Other Lipid Mediat 68–69:263–290
Li N et al (2010) Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese population. Brain Res Bull 81(1):38–42
Liu F et al (2011) Association of adiponectin gene polymorphisms with the risk of ischemic stroke in a Chinese Han population. Mol Biol Rep 38(3):1983–1988
Liu M et al (2007) Stroke in China: epidemiology, prevention, and management strategies. Lancet Neurol 6(5):456–464
MeCaskie PA et al (2008) 15-Lipoxygenase gene variants are associated with carotid plaque but not carotid intima-media thickness. Hum Genet 123(5):445–453
Obrosova IG et al (2010) Different roles of 12/15-lipoxygenase in diabetic large and small fiber peripheral and autonomic neuropathies. Am J Pathol 177(3):1436–1447
Qin X et al (2011) The RANTES gene promoter polymorphisms are associated with the risk of atherothrombotic cerebral infarction in Northern Han Chinese. Clinica Chimica Acta 412(11–12):1112–1115
Reilly KB et al (2004) 12/15-Lipoxygenase activity mediates inflammatory monocyte/ endothelial interactions and atherosclerosis in vivo. J Biol Chem 279(10):9440–9450
Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126
Taylor AM et al (2005) The effects of leukocyte-type 12/15-lipoxygenase on Id3-mediated vascular smooth muscle cell growth. Arterioscler Thromb Vasc Biol 25(10):2069–2074
Van Hee VC et al (2010) Common genetic variation, residential proximity to traffic exposure, and left ventricular mass: the multi-ethnic study of atherosclerosis. Environ Health Perspect 118(7):962–969
Wang LD et al (2005) Preventing chronic diseases in China. Lancet 366(9499):1821–1824
Wittwer J, Hersberger M (2007) The two faces of the 15-lipoxygenase in atherosclerosis. Prostaglandins Leuko Essent Fatty Acids 77(2):67–77
Wittwer J et al (2006) Functional Polymorphism in ALOX15 results in increased allele-specific transcription in macrophages through binding of the transcription factor SP1I. Hum Mutat 27(1):78–87
Wittwer J et al (2007) The c.-292C>T promoter polymorphism increases reticulocyte-type 15-lipoxygenase-1 activity and could be atheroprotective. Clin Chem Lab Med 45(4):487–492
Zhang K et al (2010) Two single nucleotide polymorphisms in ALOX15 are associated with risk of coronary artery disease in a Chinese Han population. Hear Vessel 25(5):368–373
Zhao D et al (2011) Association of apolipoprotein M gene polymorphisms with ischemic stroke in a Han Chinese population. J Mol Neurosci 43(3):370–375
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This study was supported by a grant from the National Natural Science Foundation of China (81070913).
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Zhao, J., He, Z., Ma, S. et al. Association of ALOX15 Gene Polymorphism with Ischemic Stroke in Northern Chinese Han Population. J Mol Neurosci 47, 458–464 (2012). https://doi.org/10.1007/s12031-012-9721-9
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DOI: https://doi.org/10.1007/s12031-012-9721-9