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      Relationship of Serum Interleukin-10 and Its Genetic Variations with Ischemic Stroke in a Chinese General Population

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          Abstract

          Background and Purpose

          Anti-inflammatory cytokine and its genetic variations may play an important role in the process of atherosclerosis. We assessed whether serum interleukin-10 (IL-10) and its genetic variations are associated with ischemic stroke in a Chinese general population.

          Methods

          An epidemiological survey on cardiovascular diseases and their risk factors was carried in a general population in Beijing in 2005. Serum IL-10, IL-6, p-selectin, soluble intercellular adhesion molecule-1 and C-reactive protein were analyzed using ELISA kits, while three IL-10 Single Nucleotide Polymorphisms (SNP) (rs1800872, rs1554286 and rs3021094) were genotyped in 1475 participants.

          Results

          A high serum IL-10 (top tertile) was significantly associated with ischemic stroke (multivariable adjusted odds ratio (OR) =0.50; 95%CI 0.31-0.81). Rs1800872 (AA vs. AC+CC genotype, OR=1.60; 1.06-2.39), rs1554286(TT vs. CT+CC genotype, OR=1.59; 1.06-2.39), and rs3021094 ( CC/CA vs. AA genotype, OR=1.64; 1.04-2.60) were all significantly associated with ischemic stroke even after controlling for age, sex, smoking, systolic blood pressure, total cholesterol, glucose, body mass index and serum IL-10. The SNP score (a summary index of these SNPs) and IL-10 (top tertile) together significantly improved the discriminative power in predicting ischemic stroke by 3.3% (95%CI: 0.2-6.4, p=0.0398) compared to predictions based on conventional risk factors alone.

          Conclusions

          The lower serum IL-10 concentration and its selected genetic variations were significantly associated with an increased likelihood of ischemic stroke in this cross-sectional study. Our results suggest that more prospective studies should be conducted to provide stronger evidence justifying the use of IL-10 and its SNPs as new biomarkers to identify a predisposition towards ischemic stroke.

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          Most cited references18

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          Diagnosis and classification of diabetes mellitus.

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            Protective role of interleukin-10 in atherosclerosis.

            The potential role of anti-inflammatory cytokines in the modulation of the atherosclerotic process remains unknown. Interleukin (IL)-10 has potent deactivating properties in macrophages and T cells and modulates many cellular processes that may interfere with the development and stability of the atherosclerotic plaque. IL-10 is expressed in human atherosclerosis and is associated with decreased signs of inflammation. In the present study, we show that IL-10-deficient C57BL/6J mice fed an atherogenic diet and raised under specific pathogen-free conditions exhibit a significant 3-fold increase in lipid accumulation compared with wild-type mice. Interestingly, the susceptibility of IL-10-deficient mice to atherosclerosis was exceedingly high (30-fold increase) when the mice were housed under conventional conditions. Atherosclerotic lesions of IL-10-deficient mice showed increased T-cell infiltration, abundant interferon-gamma expression, and decreased collagen content. In vivo, transfer of murine IL-10 achieved 60% reduction in lesion size. These results underscore the critical roles of IL-10 in both atherosclerotic lesion formation and stability. Moreover, IL-10 appears to be crucial as a protective factor against the effect of environmental pathogens on atherosclerosis.
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              Spliced segments at the 5' terminus of adenovirus 2 late mRNA.

              An mRNA fraction coding for hexon polypeptide, the major virion structural protein, was purified by gel electrophoresis from extracts of adenovirus 2-infected cells late in the lytic cycle. The mRNA sequences in this fraction were mapped between 51.7 and 61.3 units on the genome by visualizing RNA-DNA hybrids in the electron microscope. When hybrids of hexon mRNA and single-stranded restriction endonuclease cleavage fragments of viral DNA were visualized in the electron microscope,branched forms were observed in which 160 nucleotides of RNA from the 5' terminus were not hydrogen bonded to the single-stranded DNA. DNA sequences complementary to the RNA sequences in each 5' tail were found by electron microscopy to be located at 17, 20, and 27 units on the same strand as that coding for the body of the hexon mRNA. Thus, four segments of viral RNA may be joined together during the synthesis of mature hexon mRNA. A model is presented for adenovirus late mRNA synthesis that involves multiple splicing during maturation of a larger precursor nuclear RNA.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                11 September 2013
                : 8
                : 9
                : e74126
                Affiliations
                [1 ]Peking University Clinical Research Institute, Beijing, People’s Republic of China
                [2 ]School of Medicine and Dentistry, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, Scotland, United Kingdom
                [3 ]Norwich Research Park Cardiovascular Research Group, Norwich Medical School, University of East Anglia, Norwich, United Kingdom
                [4 ]Clinical Gerontology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
                [5 ]Stroke Research Group, Norfolk and Norwich University Hospital, Norwich, United Kingdom
                [6 ]Department of Cardiology, James Paget University Hospital, Great Yarmouth, United Kingdom
                [7 ]Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, People’s Republic of China
                [8 ]Shijingshan Center for Disease Control and Prevention, Beijing, People’s Republic of China
                [9 ]Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, People’s Republic of China
                [10 ]The George Institute, Beijing, People’s Republic of China
                University of Birmingham, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: GX. Performed the experiments: GX YL LZ PS FR YW. Analyzed the data: GX. Wrote the manuscript: GX PKM MJSZ.

                Article
                PONE-D-13-03366
                10.1371/journal.pone.0074126
                3770660
                24040186
                0839b295-9bfe-496e-881e-67ca9960c6c4
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 January 2013
                : 1 August 2013
                Funding
                This study was supported by grants 2006-yq-006 of the Young Researchers Foundation of Fuwai Hospital, grants 30471494 and 30872168 of the National Natural Science Foundation of China, and grants 2001BA703B01 of the People’s Republic of China National 10th Five-Year Plan Science and Technology Key Projects. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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