A Common 936 C/T Mutation in the Gene for Vascular Endothelial Growth Factor Is Associated with Vascular Endothelial Growth Factor Plasma Levels
Background: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3′ untranslated region (3′-UTR) of the VEGF gene and to...
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| Veröffentlicht in: | Journal of vascular research 2000-11, Vol.37 (6), p.443-448 |
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| creator | Renner, Wilfried Kotschan, Sabine Hoffmann, Christine Obermayer-Pietsch, Barbara Pilger, Ernst |
| description | Background: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3′ untranslated region (3′-UTR) of the VEGF gene and to analyze their relation to VEGF plasma levels. Methods: The complete 3′-UTR (nucleotide 700–2622) of the VEGF gene was screened for sequence variations by single-strand conformation polymorphism (SSCP) analysis. Frequencies of mutated alleles were determined in 119 healthy subjects; VEGF plasma levels were analyzed in a subgroup of 23 healthy men aged 18–36 years. Results: Three novel mutations (702 C/T, 936 C/T, 1612 G/A) were found, allele frequencies of 702T, 936T and 1612A were of 0.017, 0.160 and 0.471, respectively. VEGF plasma levels were significantly lower in carriers of the 936T allele (9.1 ± 2.7 pg/ml, mean ± SEM) than in noncarriers (28.0 ± 5.5 pg/ml, p = 0.033), whereas the 702 C/T and the 1612 G/A mutations showed no association with VEGF plasma levels. The 936 C/T exchange led to the loss of a potential binding site for transcription factor AP-4, although the functionality of this binding site remains unclear. Conclusion: We have found three common mutations in the VEGF gene; one of them, a 936 C/T exchange, may be an important determinant of VEGF plasma levels. |
| doi_str_mv | 10.1159/000054076 |
| format | Article |
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Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3′ untranslated region (3′-UTR) of the VEGF gene and to analyze their relation to VEGF plasma levels. Methods: The complete 3′-UTR (nucleotide 700–2622) of the VEGF gene was screened for sequence variations by single-strand conformation polymorphism (SSCP) analysis. Frequencies of mutated alleles were determined in 119 healthy subjects; VEGF plasma levels were analyzed in a subgroup of 23 healthy men aged 18–36 years. Results: Three novel mutations (702 C/T, 936 C/T, 1612 G/A) were found, allele frequencies of 702T, 936T and 1612A were of 0.017, 0.160 and 0.471, respectively. VEGF plasma levels were significantly lower in carriers of the 936T allele (9.1 ± 2.7 pg/ml, mean ± SEM) than in noncarriers (28.0 ± 5.5 pg/ml, p = 0.033), whereas the 702 C/T and the 1612 G/A mutations showed no association with VEGF plasma levels. The 936 C/T exchange led to the loss of a potential binding site for transcription factor AP-4, although the functionality of this binding site remains unclear. Conclusion: We have found three common mutations in the VEGF gene; one of them, a 936 C/T exchange, may be an important determinant of VEGF plasma levels.</description><identifier>ISSN: 1018-1172</identifier><identifier>EISSN: 1423-0135</identifier><identifier>DOI: 10.1159/000054076</identifier><identifier>PMID: 11146397</identifier><identifier>CODEN: JVREE9</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>3' Untranslated Regions - genetics ; Adolescent ; Adult ; Alleles ; Binding Sites ; Biological and medical sciences ; Blood vessels and receptors ; DNA Mutational Analysis ; DNA-Binding Proteins - metabolism ; Endothelial Growth Factors - blood ; Endothelial Growth Factors - genetics ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Gene Frequency ; Genes ; Genetic Variation ; Genotype ; Humans ; Lymphokines - blood ; Lymphokines - genetics ; Male ; Molecular Sequence Data ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Research Paper ; Transcription Factors - metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Vertebrates: cardiovascular system</subject><ispartof>Journal of vascular research, 2000-11, Vol.37 (6), p.443-448</ispartof><rights>2000 S. Karger AG, Basel</rights><rights>2001 INIST-CNRS</rights><rights>Copyright 2000 S. Karger AG, Basel</rights><rights>Copyright S. Karger AG Nov/Dec 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-ce4036e83d5c404c20657e53d72cda87feb58b8ae3ece484e8d6d1f0ba70c94e3</citedby><cites>FETCH-LOGICAL-c414t-ce4036e83d5c404c20657e53d72cda87feb58b8ae3ece484e8d6d1f0ba70c94e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,780,784,789,790,2429,23930,23931,25140,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=863537$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11146397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Renner, Wilfried</creatorcontrib><creatorcontrib>Kotschan, Sabine</creatorcontrib><creatorcontrib>Hoffmann, Christine</creatorcontrib><creatorcontrib>Obermayer-Pietsch, Barbara</creatorcontrib><creatorcontrib>Pilger, Ernst</creatorcontrib><title>A Common 936 C/T Mutation in the Gene for Vascular Endothelial Growth Factor Is Associated with Vascular Endothelial Growth Factor Plasma Levels</title><title>Journal of vascular research</title><addtitle>J Vasc Res</addtitle><description>Background: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3′ untranslated region (3′-UTR) of the VEGF gene and to analyze their relation to VEGF plasma levels. Methods: The complete 3′-UTR (nucleotide 700–2622) of the VEGF gene was screened for sequence variations by single-strand conformation polymorphism (SSCP) analysis. Frequencies of mutated alleles were determined in 119 healthy subjects; VEGF plasma levels were analyzed in a subgroup of 23 healthy men aged 18–36 years. Results: Three novel mutations (702 C/T, 936 C/T, 1612 G/A) were found, allele frequencies of 702T, 936T and 1612A were of 0.017, 0.160 and 0.471, respectively. VEGF plasma levels were significantly lower in carriers of the 936T allele (9.1 ± 2.7 pg/ml, mean ± SEM) than in noncarriers (28.0 ± 5.5 pg/ml, p = 0.033), whereas the 702 C/T and the 1612 G/A mutations showed no association with VEGF plasma levels. The 936 C/T exchange led to the loss of a potential binding site for transcription factor AP-4, although the functionality of this binding site remains unclear. Conclusion: We have found three common mutations in the VEGF gene; one of them, a 936 C/T exchange, may be an important determinant of VEGF plasma levels.</description><subject>3' Untranslated Regions - genetics</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Alleles</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Blood vessels and receptors</subject><subject>DNA Mutational Analysis</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Endothelial Growth Factors - blood</subject><subject>Endothelial Growth Factors - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation</subject><subject>Gene Frequency</subject><subject>Genes</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Humans</subject><subject>Lymphokines - blood</subject><subject>Lymphokines - genetics</subject><subject>Male</subject><subject>Molecular Sequence Data</subject><subject>Point Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Single-Stranded Conformational</subject><subject>Research Paper</subject><subject>Transcription Factors - metabolism</subject><subject>Vascular Endothelial Growth Factor A</subject><subject>Vascular Endothelial Growth Factors</subject><subject>Vertebrates: cardiovascular system</subject><issn>1018-1172</issn><issn>1423-0135</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqN0U1LHDEYB_BQWqpVDz0XSlAQepia10nmuCy6WrZUivU6ZJNn6tjMZE1mlH4LP7LZ7rqFUmhzScj_lyckD0JvKflIqaxOSB5SEFW-QLtUMF4QyuXLvCZUF5QqtoPepHRLCBWVLl-jHUqpKHmldtHjBE9D14UeV7zE05Mr_HkczNDmjbbHww3gGfSAmxDxtUl29Cbi096FnPjWeDyL4WG4wWfGDplcJDxJKdjWDODwQ5uT_zh16U3qDJ7DPfi0j141xic42Mx76NvZ6dX0vJh_mV1MJ_PCCiqGwoIgvATNnbSCCMtIKRVI7hSzzmjVwELqhTbAIVMtQLvS0YYsjCK2EsD30PG67jKGuxHSUHdtsuC96SGMqVZMMl1V-p-Q5b9UhFQZHv4Bb8MY-_yImjEhJZd6hT6skY0hpQhNvYxtZ-LPmpJ61cx628xs328KjosO3G-56V4GRxuQP9n4JpretmnrdMklX6l3a_XDxO8Qt_HzJYd_TT9df_0F6qVr-BNkELnb</recordid><startdate>20001101</startdate><enddate>20001101</enddate><creator>Renner, Wilfried</creator><creator>Kotschan, Sabine</creator><creator>Hoffmann, Christine</creator><creator>Obermayer-Pietsch, Barbara</creator><creator>Pilger, Ernst</creator><general>Karger</general><general>S. 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Psychology</topic><topic>Gene Expression Regulation</topic><topic>Gene Frequency</topic><topic>Genes</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Humans</topic><topic>Lymphokines - blood</topic><topic>Lymphokines - genetics</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Point Mutation</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Single-Stranded Conformational</topic><topic>Research Paper</topic><topic>Transcription Factors - metabolism</topic><topic>Vascular Endothelial Growth Factor A</topic><topic>Vascular Endothelial Growth Factors</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Renner, Wilfried</creatorcontrib><creatorcontrib>Kotschan, Sabine</creatorcontrib><creatorcontrib>Hoffmann, Christine</creatorcontrib><creatorcontrib>Obermayer-Pietsch, Barbara</creatorcontrib><creatorcontrib>Pilger, Ernst</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of vascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Renner, Wilfried</au><au>Kotschan, Sabine</au><au>Hoffmann, Christine</au><au>Obermayer-Pietsch, Barbara</au><au>Pilger, Ernst</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Common 936 C/T Mutation in the Gene for Vascular Endothelial Growth Factor Is Associated with Vascular Endothelial Growth Factor Plasma Levels</atitle><jtitle>Journal of vascular research</jtitle><addtitle>J Vasc Res</addtitle><date>2000-11-01</date><risdate>2000</risdate><volume>37</volume><issue>6</issue><spage>443</spage><epage>448</epage><pages>443-448</pages><issn>1018-1172</issn><eissn>1423-0135</eissn><coden>JVREE9</coden><abstract>Background: Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Strong interindividual variations of VEGF plasma levels have been reported previously. Aim of the present study was to search for mutations in the 3′ untranslated region (3′-UTR) of the VEGF gene and to analyze their relation to VEGF plasma levels. Methods: The complete 3′-UTR (nucleotide 700–2622) of the VEGF gene was screened for sequence variations by single-strand conformation polymorphism (SSCP) analysis. Frequencies of mutated alleles were determined in 119 healthy subjects; VEGF plasma levels were analyzed in a subgroup of 23 healthy men aged 18–36 years. Results: Three novel mutations (702 C/T, 936 C/T, 1612 G/A) were found, allele frequencies of 702T, 936T and 1612A were of 0.017, 0.160 and 0.471, respectively. VEGF plasma levels were significantly lower in carriers of the 936T allele (9.1 ± 2.7 pg/ml, mean ± SEM) than in noncarriers (28.0 ± 5.5 pg/ml, p = 0.033), whereas the 702 C/T and the 1612 G/A mutations showed no association with VEGF plasma levels. The 936 C/T exchange led to the loss of a potential binding site for transcription factor AP-4, although the functionality of this binding site remains unclear. Conclusion: We have found three common mutations in the VEGF gene; one of them, a 936 C/T exchange, may be an important determinant of VEGF plasma levels.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>11146397</pmid><doi>10.1159/000054076</doi><tpages>6</tpages></addata></record> |
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| subjects | 3' Untranslated Regions - genetics Adolescent Adult Alleles Binding Sites Biological and medical sciences Blood vessels and receptors DNA Mutational Analysis DNA-Binding Proteins - metabolism Endothelial Growth Factors - blood Endothelial Growth Factors - genetics Fundamental and applied biological sciences. Psychology Gene Expression Regulation Gene Frequency Genes Genetic Variation Genotype Humans Lymphokines - blood Lymphokines - genetics Male Molecular Sequence Data Point Mutation Polymerase Chain Reaction Polymorphism, Single-Stranded Conformational Research Paper Transcription Factors - metabolism Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Vertebrates: cardiovascular system |
| title | A Common 936 C/T Mutation in the Gene for Vascular Endothelial Growth Factor Is Associated with Vascular Endothelial Growth Factor Plasma Levels |
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