Association between Interleukin-1 Gene Single Nucleotide Polymorphisms and Ischemic Stroke Classified by TOAST Criteria in the Han Population of Northern China

Increasing evidence suggests that IL-1β (C-511T) and IL-1α (C-889T) genes polymorphisms are associated with the susceptibility to cardiocerebral vascular disease. In this paper, we investigated the relationships between these polymorphisms and the risk of ischemic stroke (IS) classified by TOAST criteria in the north Chinese Han population. 440 cases of IS and 486 age- and gender-matched controls of Chinese Han population were enrolled. Association study showed that the TT genotype and T allele of IL-1α-889 C/T were significantly associated with IS of a large artery atherosclerosis (LAA) (TT: OR = 2.01, 95% CI = 1.34–3.0, and P < 0.001; T: OR = 1.44, 95% CI = 1.18–1.78, and P = 0.001). However, there was no significant difference in the distribution of IL-1α-889 C/T genotypes and allele frequencies between the two subgroups (small-artery occlusion (SVD) and cardioembolism (CE)) of IS and control groups. No significant association was also found between the IL-1β-511 TT genotype and T allele (TT: OR = 0.79, 95% CI = 0.56–1.11, and P = 0.175; T: OR = 0.83, 95% CI = 0.68–1.01, and P = 0.066) and IS as well as subgroups of CE and SVD. Our results implicated that IL-1α-889 C/T gene polymorphism might be associated with the susceptibility to IS, especially to IS with LAA, in a north Chinese Han population.

[1]  A. Blakemore,et al.  Single base polymorphism at −511 in the human interleukin-1β gene (IL1β) , 1992 .

[2]  A. Słowik,et al.  Interleukin 1 Beta Polymorphism (–511) and Risk of Stroke due to Small Vessel Disease , 2005, Cerebrovascular Diseases.

[3]  J. Um,et al.  Functional Polymorphism of IL-1 Alpha and Its Potential Role in Obesity in Humans and Mice , 2011, PloS one.

[4]  X. Shang,et al.  Association of inflammatory response gene polymorphism with atherothrombotic stroke in Northern Han Chinese. , 2012, Acta biochimica et biophysica Sinica.

[5]  J. Um,et al.  Aspects of gene polymorphisms in cerebral infarction: inflammatory cytokines , 2005, Cellular and Molecular Life Sciences CMLS.

[6]  J. Crusius,et al.  Allelic polymorphism in IL‐1β and IL‐1 receptor antagonist (IL‐1Ra) genes in inflammatory bowel disease , 1995, Clinical and experimental immunology.

[7]  T. Ahern,et al.  The IL-6 G-174C polymorphism may be associated with ischaemic stroke in patients without a history of hypertension , 2004, Irish journal of medical science.

[8]  A. Singleton,et al.  IL1RN VNTR Polymorphism in Ischemic Stroke: Analysis in 3 Populations , 2007, Stroke.

[9]  L. Cui,et al.  Association of interleukin-1 gene cluster polymorphisms with ischemic stroke in a Chinese population. , 2006, Neurology India.

[10]  J. Um,et al.  Association of interleukin-1 alpha gene polymorphism with cerebral infarction. , 2003, Brain research. Molecular brain research.

[11]  Suzanne Cheng,et al.  Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events , 2006, Clinical chemistry and laboratory medicine.

[12]  S. Yim,et al.  Susceptibility for ischemic stroke in Korean population is associated with polymorphisms of the interleukin-1 receptor antagonist and tumor necrosis factor-α genes, but not the interleukin-1β gene , 2004, Neuroscience Letters.

[13]  M. Margaglione,et al.  Relevance of Interleukin-1 Receptor Antagonist Intron-2 Polymorphism in Ischemic Stroke , 2003, Cerebrovascular Diseases.

[14]  N. Rothwell,et al.  Cortical cell death induced by IL-1 is mediated via actions in the hypothalamus of the rat. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Um,et al.  Interleukin-1 gene cluster polymorphisms in cerebral infarction. , 2003, Cytokine.

[16]  Shumin Deng,et al.  Association of PDE4D and IL-1 gene polymorphism with ischemic stroke in a Han Chinese population , 2010, Brain Research Bulletin.

[17]  C. Rowe,et al.  Inflammation following stroke , 2006, Journal of Clinical Neuroscience.

[18]  S. Kida,et al.  Middle cerebral artery occlusion in the rat causes a biphasic production of immunoreactive interleukin-1β in the cerebral cortex , 1998, Neuroscience Letters.

[19]  John B. Shoven,et al.  I , Edinburgh Medical and Surgical Journal.

[20]  R. Levine,et al.  Interleukin-1 Receptor Signaling Mediates Atherosclerosis Associated With Bacterial Exposure and/or a High-Fat Diet in a Murine Apolipoprotein E Heterozygote Model: Pharmacotherapeutic Implications , 2004, Circulation.

[21]  N. Rothwell,et al.  Neuroprotective Effects of Human Recombinant Interleukin-1 Receptor Antagonist in Focal Cerebral Ischaemia in the Rat , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  A. Mattioli.  Polymorphism of the interleukin 1-b gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro , 2005 .

[23]  C. Mariani,et al.  Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-1α , 2002, Immunogenetics.

[24]  T. Kooistra,et al.  Cytokines and atherosclerosis: a comprehensive review of studies in mice , 2008, Cardiovascular research.

[25]  G. Assenza,et al.  A role of TNF‐α gene variant on juvenile ischemic stroke: a case–control study , 2005 .

[26]  D. Sheer,et al.  Cloning and chromosome mapping of the human interleukin-1 receptor antagonist gene. , 1992, Cytokine.

[27]  T. Yue,et al.  Concomitant cortical expression of TNF-α and IL-1β mRNAs follows early response gene expression in transient focal ischemia , 1994 .

[28]  O. Melander,et al.  Genetic Variation Within the Interleukin-1 Gene Cluster and Ischemic Stroke , 2012, Stroke.

[29]  A. Słowik,et al.  Lack of association between interleukin-1β polymorphism (−511) and ischaemic stroke , 2004 .

[30]  M. Moskowitz,et al.  Pathobiology of ischaemic stroke: an integrated view , 1999, Trends in Neurosciences.

[31]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[32]  P. Ridker,et al.  Genetic variants within the interleukin-1 gene cluster, and risk of incident myocardial infarction, and ischemic stroke: a nested case-control approach. , 2008, Atherosclerosis.

[33]  B. Ponder,et al.  Dinucleotide repeat polymorphism at the RBP3 locus in chromosome band 10q11.2. , 1992, Human molecular genetics.