Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura

Introduction:  Idiopathic thrombocytopenic purpura (ITP) is an organ‐specific autoimmune hemorrhagic disease characterized by breakdown of self‐tolerance and triggering autoreactive lymphocytes’ response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays...

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Veröffentlicht in:International journal of laboratory hematology 2012-08, Vol.34 (4), p.369-376
Hauptverfasser: EL-SHIEKH, E. H., BESSA, S. S., ABDOU, S. M., EL-REFAEY, W. A.
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creator EL-SHIEKH, E. H.
BESSA, S. S.
ABDOU, S. M.
EL-REFAEY, W. A.
description Introduction:  Idiopathic thrombocytopenic purpura (ITP) is an organ‐specific autoimmune hemorrhagic disease characterized by breakdown of self‐tolerance and triggering autoreactive lymphocytes’ response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T‐cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T‐cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP. Methods:  This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real‐time quantitative polymerase chain reaction. Plasma S‐adenosylhomocysteine (SAH) levels were assayed with reversed‐phase high‐performance liquid chromatography. Results:  DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP. Conclusions:  Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP.
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H. ; BESSA, S. S. ; ABDOU, S. M. ; EL-REFAEY, W. A.</creator><creatorcontrib>EL-SHIEKH, E. H. ; BESSA, S. S. ; ABDOU, S. M. ; EL-REFAEY, W. A.</creatorcontrib><description>Introduction:  Idiopathic thrombocytopenic purpura (ITP) is an organ‐specific autoimmune hemorrhagic disease characterized by breakdown of self‐tolerance and triggering autoreactive lymphocytes’ response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T‐cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T‐cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP. Methods:  This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real‐time quantitative polymerase chain reaction. Plasma S‐adenosylhomocysteine (SAH) levels were assayed with reversed‐phase high‐performance liquid chromatography. Results:  DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP. Conclusions:  Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP.</description><identifier>ISSN: 1751-5521</identifier><identifier>EISSN: 1751-553X</identifier><identifier>DOI: 10.1111/j.1751-553X.2012.01404.x</identifier><identifier>PMID: 22321265</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Autoimmunity ; Chromatography, High Pressure Liquid ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA methylation ; DNA methyltransferase ; DNA methyltransferase 3A ; Egypt ; epigenetics ; Etiology ; Female ; Gene expression ; Gene Expression Regulation, Enzymologic ; Hemorrhagic disease ; High-performance liquid chromatography ; Humans ; Idiopathic thrombocytopenic purpura ; Immunological tolerance ; Lymphocytes ; Lymphocytes T ; Male ; Peripheral blood mononuclear cells ; Platelets ; Polymerase Chain Reaction ; Purpura, Thrombocytopenic, Idiopathic - enzymology ; Purpura, Thrombocytopenic, Idiopathic - genetics ; RNA, Messenger - metabolism ; S-adenosylhomocysteine</subject><ispartof>International journal of laboratory hematology, 2012-08, Vol.34 (4), p.369-376</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2012 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4414-e86a54867e2776a75741f1082ec0b49655efd72d099f9e06789a04fb79989bda3</citedby><cites>FETCH-LOGICAL-c4414-e86a54867e2776a75741f1082ec0b49655efd72d099f9e06789a04fb79989bda3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1751-553X.2012.01404.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1751-553X.2012.01404.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22321265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EL-SHIEKH, E. H.</creatorcontrib><creatorcontrib>BESSA, S. S.</creatorcontrib><creatorcontrib>ABDOU, S. M.</creatorcontrib><creatorcontrib>EL-REFAEY, W. A.</creatorcontrib><title>Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura</title><title>International journal of laboratory hematology</title><addtitle>Int J Lab Hematol</addtitle><description>Introduction:  Idiopathic thrombocytopenic purpura (ITP) is an organ‐specific autoimmune hemorrhagic disease characterized by breakdown of self‐tolerance and triggering autoreactive lymphocytes’ response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T‐cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T‐cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP. Methods:  This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real‐time quantitative polymerase chain reaction. Plasma S‐adenosylhomocysteine (SAH) levels were assayed with reversed‐phase high‐performance liquid chromatography. Results:  DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP. Conclusions:  Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP.</description><subject>Adult</subject><subject>Autoimmunity</subject><subject>Chromatography, High Pressure Liquid</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA methylation</subject><subject>DNA methyltransferase</subject><subject>DNA methyltransferase 3A</subject><subject>Egypt</subject><subject>epigenetics</subject><subject>Etiology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Hemorrhagic disease</subject><subject>High-performance liquid chromatography</subject><subject>Humans</subject><subject>Idiopathic thrombocytopenic purpura</subject><subject>Immunological tolerance</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Peripheral blood mononuclear cells</subject><subject>Platelets</subject><subject>Polymerase Chain Reaction</subject><subject>Purpura, Thrombocytopenic, Idiopathic - enzymology</subject><subject>Purpura, Thrombocytopenic, Idiopathic - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>S-adenosylhomocysteine</subject><issn>1751-5521</issn><issn>1751-553X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1r3DAQhkVpadI0f6Ho2IsdSbYl-VIIm2-WLYSUhlyEbI-72tqWI2nJ-t9XzqZ7jhBomHnmHTEvQpiSlMZztkmpKGhSFNljyghlKaE5ydPdB3R8KHw8xIweoS_ebwgpRE7Kz-iIsYxRxotjNNzbDrBt8cXqHPcQ1lMXnB58C057wFlM3scK7EYH3hs7YDPgyz_TGIwe8KiDgSF4_GLCGpvG2JhZmxqHtbN9Zesp2BGGmBi3Ll79FX1qdefh9O09Qb-uLh8WN8ny5_Xt4nyZ1HlO8wQk10UuuQAmBNci_pu2lEgGNanykhcFtI1gDSnLtgTChSw1ydtKlKUsq0ZnJ-j7Xnd09nkLPqje-Bq6Tg9gt15RwiTJKOH8PSjLhORSRFTu0dpZ7x20anSm126KkJqNURs171zN-1ezMerVGLWLrd_epmyrHppD438nIvBjD7yYDqZ3C6vbu-XNHEaBZC9gfIDdQUC7v4qLTBTq9-paPa3kw8XTgiuZ_QPjwav2</recordid><startdate>201208</startdate><enddate>201208</enddate><creator>EL-SHIEKH, E. H.</creator><creator>BESSA, S. S.</creator><creator>ABDOU, S. M.</creator><creator>EL-REFAEY, W. A.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope></search><sort><creationdate>201208</creationdate><title>Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura</title><author>EL-SHIEKH, E. H. ; BESSA, S. S. ; ABDOU, S. M. ; EL-REFAEY, W. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4414-e86a54867e2776a75741f1082ec0b49655efd72d099f9e06789a04fb79989bda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Autoimmunity</topic><topic>Chromatography, High Pressure Liquid</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA methylation</topic><topic>DNA methyltransferase</topic><topic>DNA methyltransferase 3A</topic><topic>Egypt</topic><topic>epigenetics</topic><topic>Etiology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Hemorrhagic disease</topic><topic>High-performance liquid chromatography</topic><topic>Humans</topic><topic>Idiopathic thrombocytopenic purpura</topic><topic>Immunological tolerance</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Peripheral blood mononuclear cells</topic><topic>Platelets</topic><topic>Polymerase Chain Reaction</topic><topic>Purpura, Thrombocytopenic, Idiopathic - enzymology</topic><topic>Purpura, Thrombocytopenic, Idiopathic - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>S-adenosylhomocysteine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EL-SHIEKH, E. H.</creatorcontrib><creatorcontrib>BESSA, S. S.</creatorcontrib><creatorcontrib>ABDOU, S. M.</creatorcontrib><creatorcontrib>EL-REFAEY, W. A.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>International journal of laboratory hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EL-SHIEKH, E. H.</au><au>BESSA, S. S.</au><au>ABDOU, S. M.</au><au>EL-REFAEY, W. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura</atitle><jtitle>International journal of laboratory hematology</jtitle><addtitle>Int J Lab Hematol</addtitle><date>2012-08</date><risdate>2012</risdate><volume>34</volume><issue>4</issue><spage>369</spage><epage>376</epage><pages>369-376</pages><issn>1751-5521</issn><eissn>1751-553X</eissn><abstract>Introduction:  Idiopathic thrombocytopenic purpura (ITP) is an organ‐specific autoimmune hemorrhagic disease characterized by breakdown of self‐tolerance and triggering autoreactive lymphocytes’ response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T‐cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T‐cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP. Methods:  This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real‐time quantitative polymerase chain reaction. Plasma S‐adenosylhomocysteine (SAH) levels were assayed with reversed‐phase high‐performance liquid chromatography. Results:  DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP. Conclusions:  Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22321265</pmid><doi>10.1111/j.1751-553X.2012.01404.x</doi><tpages>8</tpages></addata></record>
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subjects Adult
Autoimmunity
Chromatography, High Pressure Liquid
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA methylation
DNA methyltransferase
DNA methyltransferase 3A
Egypt
epigenetics
Etiology
Female
Gene expression
Gene Expression Regulation, Enzymologic
Hemorrhagic disease
High-performance liquid chromatography
Humans
Idiopathic thrombocytopenic purpura
Immunological tolerance
Lymphocytes
Lymphocytes T
Male
Peripheral blood mononuclear cells
Platelets
Polymerase Chain Reaction
Purpura, Thrombocytopenic, Idiopathic - enzymology
Purpura, Thrombocytopenic, Idiopathic - genetics
RNA, Messenger - metabolism
S-adenosylhomocysteine
title Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura
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