Biopolym. Cell. 2014; 30(3):234-238.
Biomedicine
Association of IL8 and IL10 gene allelic variants with ischemic stroke risk and prognosis
1, 2Kucherenko A. M., 3Shulzhenko D. V., 3Kuznetsova S. M., 2Demydov S. V., 1Livshits L. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Educational and Scientific Center "Institute of Biology",
    Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
  3. SI «Institute of Gerontology of National Academy of Medical Sciences of Ukraine»
    67, Vyshgorodska Str., Kyiv, Ukraine, 04114

Abstract

Aim. Evaluating a role of IL8 gene –781 C/T, and IL10 gene –592C/A polymorphisms as genetic markers of ischemic stroke risk. Methods. A case group consisted of 183 patients with ischemic stroke, which were treated in the Brain Vascular Pathology unit of SI «Institute of Gerontology of NAMS of Ukraine». A control group included 88 healthy individuals older than 65 years without any history of ischemic stroke. Genotyping was performed using PCR followed by restriction fragment length polymorphism analysis. Results. Significantly (P < 0,05) higher frequency of IL8 –781T allele carriers in the case group (81,6 %) comparing to the control (70,1%) was revealed. –781T allele carriers have nearly 2-fold increased ischemic stroke development risk (OR = 1.886; 95 % CI: 1.041–3.417). Significantly (P < 0,05) higher frequency of IL10 gene –592C allele carriers was observed in the patients with ischemic stroke (98,2%) comparing to the control (90,7 %). The ischemic stroke development risk in such individuals is 5-fold increased (OR = 5.71; 95 % CI: 1.48–22.11). It was revealed that –592C allele homozygotes with ischemic stroke have more than 2-fold higher improvement (according to the Rankin scale) chances during the first fortnight of treatment (OR = 2,76; 95 % CI: 1,26–6,07). Conclusions. On the basis of the obtained significant differences, IL8 gene –781T and IL10 gene –592C variants may be considered the factors of ischemic stroke hereditary susceptibility. Besides, IL10 gene –592CC genotype is a genetic marker of the patients state positive dynamics during first two weeks of treatment.
Keywords: interleukin, ischemic stroke, polymorphism

References

[1] Garcia-Bonilla L, Benakis C, Moore J, Iadecola C, Anrather J. Immune mechanisms in cerebral ischemic tolerance. Front Neurosci. 2014;8:44. eCollection 2014.
[2] Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron. 2010;67(2):181-98.
[3] Daly AK, Day CP, Donaldson PT. Polymorphisms in immunoregulatory genes: towards individualized immunosuppressive therapy? Am J Pharmacogenomics. 2002;2(1):13-23.
[4] Emonts M, Hazes MJ, Houwing-Duistermaat JJ, van der Gaastde Jongh CE, de Vogel L, Han HK, Wouters JM, Laman JD, Dol hain RJ. Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study. BMC Med Genet. 2011;12:36.
[5] Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathol. 2000;10(1):113-26.
[6] Mukaida N, Shiroo M, Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989;143(4):1366-71.
[7] Stelzer G, Dalah I, Stein TI, Satanower Y, Rosen N, Nativ N, Oz-Levi D, Olender T, Belinky F, Bahir I, Krug H, Perco P, Mayer B, Kolker E, Safran M, Lancet D. In-silico human genomics with GeneCards. Hum Genomics. 2011;5(6):709-17.
[8] Hacking D, Knight JC, Rockett K, Brown H, Frampton J, Kwiatkowski DP, Hull J, Udalova IA. Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. Genes Immun. 2004;5(4):274–82.
[9] Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17(7):796-808.
[10] Eskdale J, Kube D, Tesch H, Gallagher G. Mapping of the human IL10 gene and further characterization of the 5' flanking sequence. Immunogenetics. 1997;46(2):120-8.
[11] Temple SE, Lim E, Cheong KY, Almeida CA, Price P, Ardlie KG, Waterer GW. Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae. Immunogenetics. 2003;55(9):629-32.
[12] Costa GC, da Costa Rocha MO, Moreira PR, Menezes CA, Silva MR, Gollob KJ, Dutra WO. Functional IL-10 gene polymorphism is associated with Chagas disease cardiomyopathy. J Infect Dis. 2009;199(3):451-4.
[13] Rousset F. genepop'007: a complete re-implementation of the genepop software for Windows and Linux. Mol Ecol Resour. 2008;8(1):103-6.
[14] Sullivan KM, Dean A, Soe MM. OpenEpi: a web-based epidemiologic and statistical calculator for public health. Public Health Rep. 2009;124(3):471–4.