East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina
Background:Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study...
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| Veröffentlicht in: | Circulation Journal 2020/02/25, Vol.84(3), pp.479-486 |
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| creator | Mizuno, Yuji Harada, Eisaku Kugimiya, Fumihito Shono, Makoto Kusumegi, Izumi Yoshimura, Michihiro Kinoshita, Kenji Yasue, Hirofumi |
| description | Background:Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.Methods and Results:The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P |
| doi_str_mv | 10.1253/circj.CJ-19-0989 |
| format | Article |
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The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.Methods and Results:The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH2*2group (P=0.0002). FMD decreased significantly in bothALDH2*1/*1andALDH2*2groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN.Conclusions:Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH2*1/1andALDH2*2patients with CSA.ALDH2*2attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH2*1/*1in patients with CSA.</description><identifier>ISSN: 1346-9843</identifier><identifier>ISSN: 1347-4820</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-19-0989</identifier><identifier>PMID: 32009064</identifier><language>eng</language><publisher>Japan: The Japanese Circulation Society</publisher><subject>Aged ; Aldehyde Dehydrogenase, Mitochondrial - genetics ; Angina Pectoris - drug therapy ; Angina Pectoris - ethnology ; Angina Pectoris - genetics ; Angina Pectoris - physiopathology ; Asian People - genetics ; Coronary spastic angina ; Coronary Vasospasm - drug therapy ; Coronary Vasospasm - ethnology ; Coronary Vasospasm - genetics ; Coronary Vasospasm - physiopathology ; Drug Resistance - genetics ; East Asian variant aldehyde dehydrogenase 2 genotype ; Endothelial dysfunction ; Female ; Humans ; Japan - epidemiology ; Male ; Middle Aged ; Nitrate tolerance ; Nitroglycerin ; Nitroglycerin - administration & dosage ; Nitroglycerin - adverse effects ; Polymorphism, Genetic ; Vasoconstriction - drug effects ; Vasoconstriction - genetics ; Vasodilator Agents - administration & dosage ; Vasodilator Agents - adverse effects</subject><ispartof>Circulation Journal, 2020/02/25, Vol.84(3), pp.479-486</ispartof><rights>2020 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-a352d89b879917e62cac122d7b2e58603ea09c38e549d29ad865281a790eaf033</citedby><cites>FETCH-LOGICAL-c494t-a352d89b879917e62cac122d7b2e58603ea09c38e549d29ad865281a790eaf033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32009064$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mizuno, Yuji</creatorcontrib><creatorcontrib>Harada, Eisaku</creatorcontrib><creatorcontrib>Kugimiya, Fumihito</creatorcontrib><creatorcontrib>Shono, Makoto</creatorcontrib><creatorcontrib>Kusumegi, Izumi</creatorcontrib><creatorcontrib>Yoshimura, Michihiro</creatorcontrib><creatorcontrib>Kinoshita, Kenji</creatorcontrib><creatorcontrib>Yasue, Hirofumi</creatorcontrib><title>East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina</title><title>Circulation Journal</title><addtitle>Circ J</addtitle><description>Background:Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.Methods and Results:The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH2*2group (P=0.0002). FMD decreased significantly in bothALDH2*1/*1andALDH2*2groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN.Conclusions:Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH2*1/1andALDH2*2patients with CSA.ALDH2*2attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH2*1/*1in patients with CSA.</description><subject>Aged</subject><subject>Aldehyde Dehydrogenase, Mitochondrial - genetics</subject><subject>Angina Pectoris - drug therapy</subject><subject>Angina Pectoris - ethnology</subject><subject>Angina Pectoris - genetics</subject><subject>Angina Pectoris - physiopathology</subject><subject>Asian People - genetics</subject><subject>Coronary spastic angina</subject><subject>Coronary Vasospasm - drug therapy</subject><subject>Coronary Vasospasm - ethnology</subject><subject>Coronary Vasospasm - genetics</subject><subject>Coronary Vasospasm - physiopathology</subject><subject>Drug Resistance - genetics</subject><subject>East Asian variant aldehyde dehydrogenase 2 genotype</subject><subject>Endothelial dysfunction</subject><subject>Female</subject><subject>Humans</subject><subject>Japan - epidemiology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nitrate tolerance</subject><subject>Nitroglycerin</subject><subject>Nitroglycerin - administration & dosage</subject><subject>Nitroglycerin - adverse effects</subject><subject>Polymorphism, Genetic</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasoconstriction - genetics</subject><subject>Vasodilator Agents - administration & dosage</subject><subject>Vasodilator Agents - adverse effects</subject><issn>1346-9843</issn><issn>1347-4820</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFUU1vEzEQtRAVLYE7J-Qjly1eez_sY7SkpVU_kChwtCbeSeJoY6e2I5G_wK-utwmtZPnNSG_ejN4j5FPJzktei6_GBrM-766LUhVMSfWGnJWiaotKcvb2uW4KJStxSt7HuGaMK1ard-RUcMYUa6oz8m8GMdFptOAi_Q0hY6K3Nnmz8q7P7UCnQ4-rfY_02wjBL9FBRMrpJTqf9luks79gMMwhYaR3NoVc0Ac_YABnkFpHf0Cy6FKkf2xa0c4H7yDs6c9tXm4NnbqldfCBnCxgiPjxiBPy62L20H0vbu4vr7rpTWEqVaUCRM17qeayVapsseEGTMl538451rJhAoEpIyTWleq5gl42NZcltIohLJgQE_LloLsN_nGHMemNjQaHARz6XdRc1CybOL4JYQeqCT7GgAu9DXaTT9cl02MC-jkB3V3rUukxgTzy-ai-m2-wfxn4b3kmXBwI65hgiS8ECNmKAY-KstJi_F6VXwkrCBqdeALTlJ2t</recordid><startdate>20200225</startdate><enddate>20200225</enddate><creator>Mizuno, Yuji</creator><creator>Harada, Eisaku</creator><creator>Kugimiya, Fumihito</creator><creator>Shono, Makoto</creator><creator>Kusumegi, Izumi</creator><creator>Yoshimura, Michihiro</creator><creator>Kinoshita, Kenji</creator><creator>Yasue, Hirofumi</creator><general>The Japanese Circulation Society</general><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>20200225</creationdate><title>East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina</title><author>Mizuno, Yuji ; Harada, Eisaku ; Kugimiya, Fumihito ; Shono, Makoto ; Kusumegi, Izumi ; Yoshimura, Michihiro ; Kinoshita, Kenji ; Yasue, Hirofumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-a352d89b879917e62cac122d7b2e58603ea09c38e549d29ad865281a790eaf033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Aldehyde Dehydrogenase, Mitochondrial - genetics</topic><topic>Angina Pectoris - drug therapy</topic><topic>Angina Pectoris - ethnology</topic><topic>Angina Pectoris - genetics</topic><topic>Angina Pectoris - physiopathology</topic><topic>Asian People - genetics</topic><topic>Coronary spastic angina</topic><topic>Coronary Vasospasm - drug therapy</topic><topic>Coronary Vasospasm - ethnology</topic><topic>Coronary Vasospasm - genetics</topic><topic>Coronary Vasospasm - physiopathology</topic><topic>Drug Resistance - genetics</topic><topic>East Asian variant aldehyde dehydrogenase 2 genotype</topic><topic>Endothelial dysfunction</topic><topic>Female</topic><topic>Humans</topic><topic>Japan - epidemiology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nitrate tolerance</topic><topic>Nitroglycerin</topic><topic>Nitroglycerin - administration & dosage</topic><topic>Nitroglycerin - adverse effects</topic><topic>Polymorphism, Genetic</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasoconstriction - genetics</topic><topic>Vasodilator Agents - administration & dosage</topic><topic>Vasodilator Agents - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mizuno, Yuji</creatorcontrib><creatorcontrib>Harada, Eisaku</creatorcontrib><creatorcontrib>Kugimiya, Fumihito</creatorcontrib><creatorcontrib>Shono, Makoto</creatorcontrib><creatorcontrib>Kusumegi, Izumi</creatorcontrib><creatorcontrib>Yoshimura, Michihiro</creatorcontrib><creatorcontrib>Kinoshita, Kenji</creatorcontrib><creatorcontrib>Yasue, Hirofumi</creatorcontrib><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>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mizuno, Yuji</au><au>Harada, Eisaku</au><au>Kugimiya, Fumihito</au><au>Shono, Makoto</au><au>Kusumegi, Izumi</au><au>Yoshimura, Michihiro</au><au>Kinoshita, Kenji</au><au>Yasue, Hirofumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2020-02-25</date><risdate>2020</risdate><volume>84</volume><issue>3</issue><spage>479</spage><epage>486</epage><pages>479-486</pages><issn>1346-9843</issn><issn>1347-4820</issn><eissn>1347-4820</eissn><abstract>Background:Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH2*1/*1and variantALDH2*2patients with CAD.Methods and Results:The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH2*2than in theALDH2*1/*1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH2*2group (P=0.0002). FMD decreased significantly in bothALDH2*1/*1andALDH2*2groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN.Conclusions:Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH2*1/1andALDH2*2patients with CSA.ALDH2*2attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH2*1/*1in patients with CSA.</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>32009064</pmid><doi>10.1253/circj.CJ-19-0989</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aldehyde Dehydrogenase, Mitochondrial - genetics Angina Pectoris - drug therapy Angina Pectoris - ethnology Angina Pectoris - genetics Angina Pectoris - physiopathology Asian People - genetics Coronary spastic angina Coronary Vasospasm - drug therapy Coronary Vasospasm - ethnology Coronary Vasospasm - genetics Coronary Vasospasm - physiopathology Drug Resistance - genetics East Asian variant aldehyde dehydrogenase 2 genotype Endothelial dysfunction Female Humans Japan - epidemiology Male Middle Aged Nitrate tolerance Nitroglycerin Nitroglycerin - administration & dosage Nitroglycerin - adverse effects Polymorphism, Genetic Vasoconstriction - drug effects Vasoconstriction - genetics Vasodilator Agents - administration & dosage Vasodilator Agents - adverse effects |
| title | East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina |
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