Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension
Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no re...
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| creator | Miyamoto, Yoshihiro Saito, Yoshihiko Kajiyama, Noboru Yoshimura, Michihiro Shimasaki, Yukio Nakayama, Masafumi Kamitani, Shigeki Harada, Masaki Ishikawa, Masahiro Kuwahara, Koichiro Ogawa, Emiko Hamanaka, Ichiro Takahashi, Nobuki Kaneshige, Toshihiko Teraoka, Hiroshi Akamizu, Takashi Azuma, Nobuyuki Yoshimasa, Yasunao Yoshimasa, Takaaki Itoh, Hiroshi Masuda, Izuru Yasue, Hirofumi Nakao, Kazuwa |
| description | Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyotoodds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamotoodds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto0.103 versus 0.050, P |
| doi_str_mv | 10.1161/01.HYP.32.1.3 |
| format | Article |
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Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyotoodds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamotoodds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto0.103 versus 0.050, P<0.0017; Kumamoto0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.(Hypertension. 1998;32:3-8.)</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/01.HYP.32.1.3</identifier><identifier>PMID: 9674630</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Adult ; Aged ; Alleles ; Arterial hypertension. Arterial hypotension ; Base Sequence ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Confidence Intervals ; Data Interpretation, Statistical ; Endothelium, Vascular - enzymology ; Exons - genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension - genetics ; Hypertension - metabolism ; Introns - genetics ; Japan ; Male ; Medical sciences ; Middle Aged ; Molecular Sequence Data ; Nitric Oxide - metabolism ; Nitric Oxide Synthase - genetics ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Repetitive Sequences, Nucleic Acid - genetics</subject><ispartof>Hypertension (Dallas, Tex. 1979), 1998-07, Vol.32 (1), p.3-8</ispartof><rights>1998 American Heart Association, Inc.</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4402-8736304ac81449fb1dfd2a4d0b6cff0e218674a6a739761cbd545784e3685c7e3</citedby><cites>FETCH-LOGICAL-c4402-8736304ac81449fb1dfd2a4d0b6cff0e218674a6a739761cbd545784e3685c7e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>310,311,315,781,785,790,791,3688,23935,23936,25145,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2337683$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9674630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyamoto, Yoshihiro</creatorcontrib><creatorcontrib>Saito, Yoshihiko</creatorcontrib><creatorcontrib>Kajiyama, Noboru</creatorcontrib><creatorcontrib>Yoshimura, Michihiro</creatorcontrib><creatorcontrib>Shimasaki, Yukio</creatorcontrib><creatorcontrib>Nakayama, Masafumi</creatorcontrib><creatorcontrib>Kamitani, Shigeki</creatorcontrib><creatorcontrib>Harada, Masaki</creatorcontrib><creatorcontrib>Ishikawa, Masahiro</creatorcontrib><creatorcontrib>Kuwahara, Koichiro</creatorcontrib><creatorcontrib>Ogawa, Emiko</creatorcontrib><creatorcontrib>Hamanaka, Ichiro</creatorcontrib><creatorcontrib>Takahashi, Nobuki</creatorcontrib><creatorcontrib>Kaneshige, Toshihiko</creatorcontrib><creatorcontrib>Teraoka, Hiroshi</creatorcontrib><creatorcontrib>Akamizu, Takashi</creatorcontrib><creatorcontrib>Azuma, Nobuyuki</creatorcontrib><creatorcontrib>Yoshimasa, Yasunao</creatorcontrib><creatorcontrib>Yoshimasa, Takaaki</creatorcontrib><creatorcontrib>Itoh, Hiroshi</creatorcontrib><creatorcontrib>Masuda, Izuru</creatorcontrib><creatorcontrib>Yasue, Hirofumi</creatorcontrib><creatorcontrib>Nakao, Kazuwa</creatorcontrib><title>Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyotoodds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamotoodds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto0.103 versus 0.050, P<0.0017; Kumamoto0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.(Hypertension. 1998;32:3-8.)</description><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Confidence Intervals</subject><subject>Data Interpretation, Statistical</subject><subject>Endothelium, Vascular - enzymology</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hypertension - genetics</subject><subject>Hypertension - metabolism</subject><subject>Introns - genetics</subject><subject>Japan</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Odds Ratio</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Repetitive Sequences, Nucleic Acid - genetics</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kM1vEzEQxS0EKmnhyBFpD4jbLv5a23usqtBUqmglQIA4WI53VmtwdlOPQ8l_X0eJOpfRzPz09OYR8o7RhjHFPlHWrH7dN4I3rBEvyIK1XNayVeIlWVDWybpj7Odrco74h1ImpdRn5KxTWipBF-T3curnPEIMLlZfQk7BV3f_Qw_V1_2UR4dQXcME1Q1W9zOGHP5B3FeXiLMPLkNf_Qh5rJaIMOWDxGq_hZRhwjBPb8irwUWEt6d-Qb5_Xn67WtW3d9c3V5e3tZeS8tpoUaxI501x1w1r1g89d7Kna-WHgQJnprh1ymnRacX8um9lq40EoUzrNYgL8vGou03zww4w201ADzG6CeYdWlP-bkUrC1gfQZ9mxASD3aawcWlvGbWHMC1ltoRpBbfMisK_Pwnv1hvon-lTeuX-4XR36F0ckpt8wGeMC6GVOcjII_Y4xwwJ_8bdIyQ7got5tLSU5MrUrOsM1WWqDysungDAwYvU</recordid><startdate>199807</startdate><enddate>199807</enddate><creator>Miyamoto, Yoshihiro</creator><creator>Saito, Yoshihiko</creator><creator>Kajiyama, Noboru</creator><creator>Yoshimura, Michihiro</creator><creator>Shimasaki, Yukio</creator><creator>Nakayama, Masafumi</creator><creator>Kamitani, Shigeki</creator><creator>Harada, Masaki</creator><creator>Ishikawa, Masahiro</creator><creator>Kuwahara, Koichiro</creator><creator>Ogawa, Emiko</creator><creator>Hamanaka, Ichiro</creator><creator>Takahashi, Nobuki</creator><creator>Kaneshige, Toshihiko</creator><creator>Teraoka, Hiroshi</creator><creator>Akamizu, Takashi</creator><creator>Azuma, Nobuyuki</creator><creator>Yoshimasa, Yasunao</creator><creator>Yoshimasa, Takaaki</creator><creator>Itoh, Hiroshi</creator><creator>Masuda, Izuru</creator><creator>Yasue, Hirofumi</creator><creator>Nakao, Kazuwa</creator><general>American Heart Association, Inc</general><general>Lippincott</general><scope>IQODW</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></search><sort><creationdate>199807</creationdate><title>Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension</title><author>Miyamoto, Yoshihiro ; Saito, Yoshihiko ; Kajiyama, Noboru ; Yoshimura, Michihiro ; Shimasaki, Yukio ; Nakayama, Masafumi ; Kamitani, Shigeki ; Harada, Masaki ; Ishikawa, Masahiro ; Kuwahara, Koichiro ; Ogawa, Emiko ; Hamanaka, Ichiro ; Takahashi, Nobuki ; Kaneshige, Toshihiko ; Teraoka, Hiroshi ; Akamizu, Takashi ; Azuma, Nobuyuki ; Yoshimasa, Yasunao ; Yoshimasa, Takaaki ; Itoh, Hiroshi ; Masuda, Izuru ; Yasue, Hirofumi ; Nakao, Kazuwa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4402-8736304ac81449fb1dfd2a4d0b6cff0e218674a6a739761cbd545784e3685c7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>Confidence Intervals</topic><topic>Data Interpretation, Statistical</topic><topic>Endothelium, Vascular - enzymology</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hypertension - genetics</topic><topic>Hypertension - metabolism</topic><topic>Introns - genetics</topic><topic>Japan</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Odds Ratio</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Repetitive Sequences, Nucleic Acid - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyamoto, Yoshihiro</creatorcontrib><creatorcontrib>Saito, Yoshihiko</creatorcontrib><creatorcontrib>Kajiyama, Noboru</creatorcontrib><creatorcontrib>Yoshimura, Michihiro</creatorcontrib><creatorcontrib>Shimasaki, Yukio</creatorcontrib><creatorcontrib>Nakayama, Masafumi</creatorcontrib><creatorcontrib>Kamitani, Shigeki</creatorcontrib><creatorcontrib>Harada, Masaki</creatorcontrib><creatorcontrib>Ishikawa, Masahiro</creatorcontrib><creatorcontrib>Kuwahara, Koichiro</creatorcontrib><creatorcontrib>Ogawa, Emiko</creatorcontrib><creatorcontrib>Hamanaka, Ichiro</creatorcontrib><creatorcontrib>Takahashi, Nobuki</creatorcontrib><creatorcontrib>Kaneshige, Toshihiko</creatorcontrib><creatorcontrib>Teraoka, Hiroshi</creatorcontrib><creatorcontrib>Akamizu, Takashi</creatorcontrib><creatorcontrib>Azuma, Nobuyuki</creatorcontrib><creatorcontrib>Yoshimasa, Yasunao</creatorcontrib><creatorcontrib>Yoshimasa, Takaaki</creatorcontrib><creatorcontrib>Itoh, Hiroshi</creatorcontrib><creatorcontrib>Masuda, Izuru</creatorcontrib><creatorcontrib>Yasue, Hirofumi</creatorcontrib><creatorcontrib>Nakao, Kazuwa</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>MEDLINE - Academic</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyamoto, Yoshihiro</au><au>Saito, Yoshihiko</au><au>Kajiyama, Noboru</au><au>Yoshimura, Michihiro</au><au>Shimasaki, Yukio</au><au>Nakayama, Masafumi</au><au>Kamitani, Shigeki</au><au>Harada, Masaki</au><au>Ishikawa, Masahiro</au><au>Kuwahara, Koichiro</au><au>Ogawa, Emiko</au><au>Hamanaka, Ichiro</au><au>Takahashi, Nobuki</au><au>Kaneshige, Toshihiko</au><au>Teraoka, Hiroshi</au><au>Akamizu, Takashi</au><au>Azuma, Nobuyuki</au><au>Yoshimasa, Yasunao</au><au>Yoshimasa, Takaaki</au><au>Itoh, Hiroshi</au><au>Masuda, Izuru</au><au>Yasue, Hirofumi</au><au>Nakao, Kazuwa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>1998-07</date><risdate>1998</risdate><volume>32</volume><issue>1</issue><spage>3</spage><epage>8</epage><pages>3-8</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>Essential hypertension has a genetic basis. Accumulating evidence, including findings of elevation of arterial blood pressure in mice lacking the endothelial nitric oxide synthase (eNOS) gene, strongly suggests that alteration in NO metabolism is implicated in hypertension. There are, however, no reports indicating that polymorphism in the eNOS gene is associated with essential hypertension. We have identified a missense variant, Glu298Asp, in exon 7 of the eNOS gene and demonstrated that it is associated with both coronary spastic angina and myocardial infarction. To explore the genetic involvement of the eNOS gene in essential hypertension, we examined the possible association between essential hypertension and several polymorphisms including the Glu298Asp variant, variable number tandem repeats in intron 4 (eNOS4b/4a), and two polymorphisms in introns 18 and 23. We performed a large-scale study of genetic association using two independent populations from Kyoto (n=458; 240 normotensive versus 218 hypertensive subjects) and Kumamoto (n=421; 223 normotensive versus 187 hypertensive subjects), Japan. In both groups, a new coding variant, Glu298Asp, showed a strong association with essential hypertension (Kyotoodds ratio, 2.3 [95% confidence interval, 1.4 to 3.9]; Kumamotoodds ratio, 2.4 [95% confidence interval, 1.4 to 4.0]). The allele frequencies of 298Asp in hypertensive subjects were significantly higher than those in normotensive subjects in both groups (Kyoto0.103 versus 0.050, P<0.0017; Kumamoto0.120 versus 0.058, P<0.0013, respectively). No such disequilibrium between genotypes was significantly associated with any other polymorphisms we examined; the Glu298Asp variant was also not linked to any other polymorphisms. In conclusion, the Glu298Asp missense variant was significantly associated with essential hypertension, which suggests that it is a genetic susceptibility factor for essential hypertension.(Hypertension. 1998;32:3-8.)</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>9674630</pmid><doi>10.1161/01.HYP.32.1.3</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Hypertension (Dallas, Tex. 1979), 1998-07, Vol.32 (1), p.3-8 |
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| subjects | Adult Aged Alleles Arterial hypertension. Arterial hypotension Base Sequence Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Clinical manifestations. Epidemiology. Investigative techniques. Etiology Confidence Intervals Data Interpretation, Statistical Endothelium, Vascular - enzymology Exons - genetics Female Gene Frequency Genotype Humans Hypertension - genetics Hypertension - metabolism Introns - genetics Japan Male Medical sciences Middle Aged Molecular Sequence Data Nitric Oxide - metabolism Nitric Oxide Synthase - genetics Odds Ratio Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Restriction Fragment Length Repetitive Sequences, Nucleic Acid - genetics |
| title | Endothelial Nitric Oxide Synthase Gene Is Positively Associated With Essential Hypertension |
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