A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease
Background Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10–20% develop peptic ulcers and
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| Veröffentlicht in: | Helicobacter (Cambridge, Mass.) Mass.), 2013-02, Vol.18 (1), p.13-21 |
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| container_title | Helicobacter (Cambridge, Mass.) |
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| creator | Yang, Chin-An Scheibenbogen, Carmen Bauer, Sandra Kleinle, Christoph Wex, Thomas Bornschein, Jan Malfertheiner, Peter Hellmig, Stephan Schumann, Ralf R. Hamann, Lutz |
| description | Background
Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10–20% develop peptic ulcers and |
| doi_str_mv | 10.1111/hel.12001 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1285098972</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1273500826</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3961-50cb5566ac089f52fbc9f9f980f066a9956ff985fff05d61dc36e6878c164ae73</originalsourceid><addsrcrecordid>eNqNkc1uGyEUhUdVq-anXfQFKpbtggQGw8wsHTe2o1huVLnJEmHmItMwwxSwUj9MnqLv0WcqiZPsKhUWXOA7R7r3FMUHSk5oXqcbcCe0JIS-Kg4pLxnmrKpf55rUDI9Y3RwURzH-IIRwNmreFgclI6Kio_KwuB-jaYCfW-gTWnnn8MLeAvoGGobkA6JoBj2gK-92nQ_DxsYOjY0BnSJaXmKk-hatsAbn0MV0if_8RlfBt1udrO8fP21E4xi9tipBi-5s2qA5OKv9WukEAQ0754PFts-iDMxUTMFq9MVGUBHeFW-MchHeP53Hxffp-Woyx4uvs4vJeIE1awTFnOg150IoTerG8NKsdWPyrokh-bVpuDD5xo0xhLeCtpoJEHVVaypGCip2XHza-w7B51nEJDsbH7pSPfhtlLSsOWnqpir_A60YJ6QuRUY_71EdfIwBjByC7VTYSUrkQ3AyBycfg8vsxyfb7bqD9oV8TioDp3vgzjrY_dtJzs8Xz5Z4r7Axwa8XhQq3UlSs4vJmOZNn19c37PKMyQn7CyvpsZQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1273500826</pqid></control><display><type>article</type><title>A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Yang, Chin-An ; Scheibenbogen, Carmen ; Bauer, Sandra ; Kleinle, Christoph ; Wex, Thomas ; Bornschein, Jan ; Malfertheiner, Peter ; Hellmig, Stephan ; Schumann, Ralf R. ; Hamann, Lutz</creator><creatorcontrib>Yang, Chin-An ; Scheibenbogen, Carmen ; Bauer, Sandra ; Kleinle, Christoph ; Wex, Thomas ; Bornschein, Jan ; Malfertheiner, Peter ; Hellmig, Stephan ; Schumann, Ralf R. ; Hamann, Lutz</creatorcontrib><description>Background
Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10–20% develop peptic ulcers and <3% progress to gastric cancer (GC). Th1‐predominant immune responses have been suggested to underlie H. pylori‐induced gastric diseases. However, the reason for a strong inter‐individual variation of susceptibility and course of the disease is currently far from being understood. It has been shown that H. pylori stimulates the host's Toll‐like receptor (TLR) 2/1 complex. Furthermore, the single nucleotide polymorphism (SNP) I602S of TLR1 alters the inflammatory cytokine response of monocytes. Therefore, we hypothesized an association of this TLR1 SNP with H. pylori‐mediated gastric pathologies.
Materials and Methods
Subjects with different TLR1 genotypes were analyzed for their IFN‐γ response of NK‐ and T‐cells. We further genotyped 548 patients with gastric diseases for this SNP and compared patients with gastritis with those having ulcer, and patients with high‐risk gastritis versus patients with GC.
Results
Homozygous 602S allele carriers exhibited impaired in vitro IFN‐γ responses to the TLR2/1 agonist Pam3CSK4. The TLR1 I602S SNP is significantly associated with GC (p = .002) and gastric ulcer (p = .051). Odds ratios showed significantly reduced risk regarding GC and peptic ulcer for the homozygous mutated genotype. The odds ratios were 0.4 (95% CI, 0.22–0.72) and 0.588 (95% CI, 0.35–1.00), respectively.
Conclusion
In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of H. pylori‐induced gastric diseases, probably via diminished Th1 responses.</description><identifier>ISSN: 1083-4389</identifier><identifier>EISSN: 1523-5378</identifier><identifier>DOI: 10.1111/hel.12001</identifier><identifier>PMID: 23067142</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Cytokines ; Female ; gamma -Interferon ; Gastric cancer ; Gastritis ; Gene polymorphism ; genetic susceptibility ; Genotype ; Guanylate cyclase ; Helicobacter Infections - immunology ; Helicobacter Infections - pathology ; Helicobacter pylori ; Helicobacter pylori - pathogenicity ; Helper cells ; Humans ; Immune response ; Inflammation ; Interferon-gamma - secretion ; Killer Cells, Natural - immunology ; Lymphocytes T ; Male ; Middle Aged ; Monocytes ; peptic ulcer ; peptic ulcers ; Polymorphism, Single Nucleotide ; Risk factors ; Risk groups ; Single-nucleotide polymorphism ; Stomach Diseases - immunology ; Stomach Diseases - pathology ; T-Lymphocytes - immunology ; TLR1 protein ; TLR2 protein ; Toll-Like Receptor 1 - genetics ; Toll-Like Receptor 1 - immunology ; Toll-like receptors ; Ulcers</subject><ispartof>Helicobacter (Cambridge, Mass.), 2013-02, Vol.18 (1), p.13-21</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2012 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3961-50cb5566ac089f52fbc9f9f980f066a9956ff985fff05d61dc36e6878c164ae73</citedby><cites>FETCH-LOGICAL-c3961-50cb5566ac089f52fbc9f9f980f066a9956ff985fff05d61dc36e6878c164ae73</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%2Fhel.12001$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhel.12001$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,27911,27912,45561,45562</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23067142$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Chin-An</creatorcontrib><creatorcontrib>Scheibenbogen, Carmen</creatorcontrib><creatorcontrib>Bauer, Sandra</creatorcontrib><creatorcontrib>Kleinle, Christoph</creatorcontrib><creatorcontrib>Wex, Thomas</creatorcontrib><creatorcontrib>Bornschein, Jan</creatorcontrib><creatorcontrib>Malfertheiner, Peter</creatorcontrib><creatorcontrib>Hellmig, Stephan</creatorcontrib><creatorcontrib>Schumann, Ralf R.</creatorcontrib><creatorcontrib>Hamann, Lutz</creatorcontrib><title>A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease</title><title>Helicobacter (Cambridge, Mass.)</title><addtitle>Helicobacter</addtitle><description>Background
Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10–20% develop peptic ulcers and <3% progress to gastric cancer (GC). Th1‐predominant immune responses have been suggested to underlie H. pylori‐induced gastric diseases. However, the reason for a strong inter‐individual variation of susceptibility and course of the disease is currently far from being understood. It has been shown that H. pylori stimulates the host's Toll‐like receptor (TLR) 2/1 complex. Furthermore, the single nucleotide polymorphism (SNP) I602S of TLR1 alters the inflammatory cytokine response of monocytes. Therefore, we hypothesized an association of this TLR1 SNP with H. pylori‐mediated gastric pathologies.
Materials and Methods
Subjects with different TLR1 genotypes were analyzed for their IFN‐γ response of NK‐ and T‐cells. We further genotyped 548 patients with gastric diseases for this SNP and compared patients with gastritis with those having ulcer, and patients with high‐risk gastritis versus patients with GC.
Results
Homozygous 602S allele carriers exhibited impaired in vitro IFN‐γ responses to the TLR2/1 agonist Pam3CSK4. The TLR1 I602S SNP is significantly associated with GC (p = .002) and gastric ulcer (p = .051). Odds ratios showed significantly reduced risk regarding GC and peptic ulcer for the homozygous mutated genotype. The odds ratios were 0.4 (95% CI, 0.22–0.72) and 0.588 (95% CI, 0.35–1.00), respectively.
Conclusion
In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of H. pylori‐induced gastric diseases, probably via diminished Th1 responses.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cytokines</subject><subject>Female</subject><subject>gamma -Interferon</subject><subject>Gastric cancer</subject><subject>Gastritis</subject><subject>Gene polymorphism</subject><subject>genetic susceptibility</subject><subject>Genotype</subject><subject>Guanylate cyclase</subject><subject>Helicobacter Infections - immunology</subject><subject>Helicobacter Infections - pathology</subject><subject>Helicobacter pylori</subject><subject>Helicobacter pylori - pathogenicity</subject><subject>Helper cells</subject><subject>Humans</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>Interferon-gamma - secretion</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monocytes</subject><subject>peptic ulcer</subject><subject>peptic ulcers</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk factors</subject><subject>Risk groups</subject><subject>Single-nucleotide polymorphism</subject><subject>Stomach Diseases - immunology</subject><subject>Stomach Diseases - pathology</subject><subject>T-Lymphocytes - immunology</subject><subject>TLR1 protein</subject><subject>TLR2 protein</subject><subject>Toll-Like Receptor 1 - genetics</subject><subject>Toll-Like Receptor 1 - immunology</subject><subject>Toll-like receptors</subject><subject>Ulcers</subject><issn>1083-4389</issn><issn>1523-5378</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uGyEUhUdVq-anXfQFKpbtggQGw8wsHTe2o1huVLnJEmHmItMwwxSwUj9MnqLv0WcqiZPsKhUWXOA7R7r3FMUHSk5oXqcbcCe0JIS-Kg4pLxnmrKpf55rUDI9Y3RwURzH-IIRwNmreFgclI6Kio_KwuB-jaYCfW-gTWnnn8MLeAvoGGobkA6JoBj2gK-92nQ_DxsYOjY0BnSJaXmKk-hatsAbn0MV0if_8RlfBt1udrO8fP21E4xi9tipBi-5s2qA5OKv9WukEAQ0754PFts-iDMxUTMFq9MVGUBHeFW-MchHeP53Hxffp-Woyx4uvs4vJeIE1awTFnOg150IoTerG8NKsdWPyrokh-bVpuDD5xo0xhLeCtpoJEHVVaypGCip2XHza-w7B51nEJDsbH7pSPfhtlLSsOWnqpir_A60YJ6QuRUY_71EdfIwBjByC7VTYSUrkQ3AyBycfg8vsxyfb7bqD9oV8TioDp3vgzjrY_dtJzs8Xz5Z4r7Axwa8XhQq3UlSs4vJmOZNn19c37PKMyQn7CyvpsZQ</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Yang, Chin-An</creator><creator>Scheibenbogen, Carmen</creator><creator>Bauer, Sandra</creator><creator>Kleinle, Christoph</creator><creator>Wex, Thomas</creator><creator>Bornschein, Jan</creator><creator>Malfertheiner, Peter</creator><creator>Hellmig, Stephan</creator><creator>Schumann, Ralf R.</creator><creator>Hamann, Lutz</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>7QL</scope><scope>C1K</scope></search><sort><creationdate>201302</creationdate><title>A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease</title><author>Yang, Chin-An ; Scheibenbogen, Carmen ; Bauer, Sandra ; Kleinle, Christoph ; Wex, Thomas ; Bornschein, Jan ; Malfertheiner, Peter ; Hellmig, Stephan ; Schumann, Ralf R. ; Hamann, Lutz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3961-50cb5566ac089f52fbc9f9f980f066a9956ff985fff05d61dc36e6878c164ae73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cytokines</topic><topic>Female</topic><topic>gamma -Interferon</topic><topic>Gastric cancer</topic><topic>Gastritis</topic><topic>Gene polymorphism</topic><topic>genetic susceptibility</topic><topic>Genotype</topic><topic>Guanylate cyclase</topic><topic>Helicobacter Infections - immunology</topic><topic>Helicobacter Infections - pathology</topic><topic>Helicobacter pylori</topic><topic>Helicobacter pylori - pathogenicity</topic><topic>Helper cells</topic><topic>Humans</topic><topic>Immune response</topic><topic>Inflammation</topic><topic>Interferon-gamma - secretion</topic><topic>Killer Cells, Natural - immunology</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monocytes</topic><topic>peptic ulcer</topic><topic>peptic ulcers</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk factors</topic><topic>Risk groups</topic><topic>Single-nucleotide polymorphism</topic><topic>Stomach Diseases - immunology</topic><topic>Stomach Diseases - pathology</topic><topic>T-Lymphocytes - immunology</topic><topic>TLR1 protein</topic><topic>TLR2 protein</topic><topic>Toll-Like Receptor 1 - genetics</topic><topic>Toll-Like Receptor 1 - immunology</topic><topic>Toll-like receptors</topic><topic>Ulcers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Chin-An</creatorcontrib><creatorcontrib>Scheibenbogen, Carmen</creatorcontrib><creatorcontrib>Bauer, Sandra</creatorcontrib><creatorcontrib>Kleinle, Christoph</creatorcontrib><creatorcontrib>Wex, Thomas</creatorcontrib><creatorcontrib>Bornschein, Jan</creatorcontrib><creatorcontrib>Malfertheiner, Peter</creatorcontrib><creatorcontrib>Hellmig, Stephan</creatorcontrib><creatorcontrib>Schumann, Ralf R.</creatorcontrib><creatorcontrib>Hamann, Lutz</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Helicobacter (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Chin-An</au><au>Scheibenbogen, Carmen</au><au>Bauer, Sandra</au><au>Kleinle, Christoph</au><au>Wex, Thomas</au><au>Bornschein, Jan</au><au>Malfertheiner, Peter</au><au>Hellmig, Stephan</au><au>Schumann, Ralf R.</au><au>Hamann, Lutz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease</atitle><jtitle>Helicobacter (Cambridge, Mass.)</jtitle><addtitle>Helicobacter</addtitle><date>2013-02</date><risdate>2013</risdate><volume>18</volume><issue>1</issue><spage>13</spage><epage>21</epage><pages>13-21</pages><issn>1083-4389</issn><eissn>1523-5378</eissn><abstract>Background
Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10–20% develop peptic ulcers and <3% progress to gastric cancer (GC). Th1‐predominant immune responses have been suggested to underlie H. pylori‐induced gastric diseases. However, the reason for a strong inter‐individual variation of susceptibility and course of the disease is currently far from being understood. It has been shown that H. pylori stimulates the host's Toll‐like receptor (TLR) 2/1 complex. Furthermore, the single nucleotide polymorphism (SNP) I602S of TLR1 alters the inflammatory cytokine response of monocytes. Therefore, we hypothesized an association of this TLR1 SNP with H. pylori‐mediated gastric pathologies.
Materials and Methods
Subjects with different TLR1 genotypes were analyzed for their IFN‐γ response of NK‐ and T‐cells. We further genotyped 548 patients with gastric diseases for this SNP and compared patients with gastritis with those having ulcer, and patients with high‐risk gastritis versus patients with GC.
Results
Homozygous 602S allele carriers exhibited impaired in vitro IFN‐γ responses to the TLR2/1 agonist Pam3CSK4. The TLR1 I602S SNP is significantly associated with GC (p = .002) and gastric ulcer (p = .051). Odds ratios showed significantly reduced risk regarding GC and peptic ulcer for the homozygous mutated genotype. The odds ratios were 0.4 (95% CI, 0.22–0.72) and 0.588 (95% CI, 0.35–1.00), respectively.
Conclusion
In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of H. pylori‐induced gastric diseases, probably via diminished Th1 responses.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23067142</pmid><doi>10.1111/hel.12001</doi><tpages>9</tpages></addata></record> |
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| ispartof | Helicobacter (Cambridge, Mass.), 2013-02, Vol.18 (1), p.13-21 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Aged Aged, 80 and over Cytokines Female gamma -Interferon Gastric cancer Gastritis Gene polymorphism genetic susceptibility Genotype Guanylate cyclase Helicobacter Infections - immunology Helicobacter Infections - pathology Helicobacter pylori Helicobacter pylori - pathogenicity Helper cells Humans Immune response Inflammation Interferon-gamma - secretion Killer Cells, Natural - immunology Lymphocytes T Male Middle Aged Monocytes peptic ulcer peptic ulcers Polymorphism, Single Nucleotide Risk factors Risk groups Single-nucleotide polymorphism Stomach Diseases - immunology Stomach Diseases - pathology T-Lymphocytes - immunology TLR1 protein TLR2 protein Toll-Like Receptor 1 - genetics Toll-Like Receptor 1 - immunology Toll-like receptors Ulcers |
| title | A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease |
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