Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension
Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an α/β heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an α-adducin polymorphism (Gly 460 Trp) is involved in esse...
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| Veröffentlicht in: | The Lancet (British edition) 1997-05, Vol.349 (9062), p.1353-1357 |
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| creator | Cusi, Daniele Barlassina, Cristina Azzani, Tiziana Casari, Girgio Citterio, Lorena Devoto, Marcella Glorioso, Nicola Lanzani, Chiara Manunta, Paolo Righetti, Marco Rivera, Rodolfo Stella, Paola Troffa, Chiara Zagato, Laura Bianchi, Giuseppe |
| description | Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an α/β heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an α-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations.
Linkage analysis of three DNA markers at different distances from the α-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the α-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp α-adducin allele.
Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9·1%, 6·5%, and 4·7%) and the significance level for linkage (p=0·0006, p=0·0119, and p=0·0211) both decreased with increasing distance from the α-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p=0·0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15·9 [SE 2·0] vs 7·4 [1·3] mm Hg; p=0·001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14·7 [2·2] vs 6·8 [1·4] mm Hg; p=0·002).
Our findings of significant linkage of the α-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that α-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the α-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium. |
| doi_str_mv | 10.1016/S0140-6736(97)01029-5 |
| format | Article |
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Linkage analysis of three DNA markers at different distances from the α-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the α-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp α-adducin allele.
Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9·1%, 6·5%, and 4·7%) and the significance level for linkage (p=0·0006, p=0·0119, and p=0·0211) both decreased with increasing distance from the α-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p=0·0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15·9 [SE 2·0] vs 7·4 [1·3] mm Hg; p=0·001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14·7 [2·2] vs 6·8 [1·4] mm Hg; p=0·002).
Our findings of significant linkage of the α-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that α-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the α-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(97)01029-5</identifier><identifier>PMID: 9149697</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Aged ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood ; Blood and lymphatic vessels ; Calmodulin-Binding Proteins - genetics ; Cardiology. Vascular system ; Case-Control Studies ; Chromosome Mapping ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; France ; Gene Frequency ; Genes ; Genetic Carrier Screening ; Genetic Markers ; Humans ; Hypertension ; Hypertension - genetics ; Hypertension - metabolism ; Ion transport ; Medical sciences ; Middle Aged ; Mutation ; Mutation - genetics ; Polymorphism, Genetic ; Proteins ; Salts ; Sodium ; Sodium Chloride, Dietary - adverse effects ; Sodium Chloride, Dietary - metabolism</subject><ispartof>The Lancet (British edition), 1997-05, Vol.349 (9062), p.1353-1357</ispartof><rights>1997 Elsevier Ltd</rights><rights>1997 INIST-CNRS</rights><rights>Copyright Lancet Ltd. May 10, 1997</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-26ea382149c8df7a2d0fcd77b305558ed0e2cab3ec2938fd894b6866843740723</citedby><cites>FETCH-LOGICAL-c416t-26ea382149c8df7a2d0fcd77b305558ed0e2cab3ec2938fd894b6866843740723</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/199064609?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2660304$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9149697$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cusi, Daniele</creatorcontrib><creatorcontrib>Barlassina, Cristina</creatorcontrib><creatorcontrib>Azzani, Tiziana</creatorcontrib><creatorcontrib>Casari, Girgio</creatorcontrib><creatorcontrib>Citterio, Lorena</creatorcontrib><creatorcontrib>Devoto, Marcella</creatorcontrib><creatorcontrib>Glorioso, Nicola</creatorcontrib><creatorcontrib>Lanzani, Chiara</creatorcontrib><creatorcontrib>Manunta, Paolo</creatorcontrib><creatorcontrib>Righetti, Marco</creatorcontrib><creatorcontrib>Rivera, Rodolfo</creatorcontrib><creatorcontrib>Stella, Paola</creatorcontrib><creatorcontrib>Troffa, Chiara</creatorcontrib><creatorcontrib>Zagato, Laura</creatorcontrib><creatorcontrib>Bianchi, Giuseppe</creatorcontrib><title>Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an α/β heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an α-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations.
Linkage analysis of three DNA markers at different distances from the α-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the α-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp α-adducin allele.
Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9·1%, 6·5%, and 4·7%) and the significance level for linkage (p=0·0006, p=0·0119, and p=0·0211) both decreased with increasing distance from the α-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p=0·0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15·9 [SE 2·0] vs 7·4 [1·3] mm Hg; p=0·001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14·7 [2·2] vs 6·8 [1·4] mm Hg; p=0·002).
Our findings of significant linkage of the α-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that α-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the α-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium.</description><subject>Aged</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Blood and lymphatic vessels</subject><subject>Calmodulin-Binding Proteins - genetics</subject><subject>Cardiology. Vascular system</subject><subject>Case-Control Studies</subject><subject>Chromosome Mapping</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>France</subject><subject>Gene Frequency</subject><subject>Genes</subject><subject>Genetic Carrier Screening</subject><subject>Genetic Markers</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - genetics</subject><subject>Hypertension - metabolism</subject><subject>Ion transport</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Polymorphism, Genetic</subject><subject>Proteins</subject><subject>Salts</subject><subject>Sodium</subject><subject>Sodium Chloride, Dietary - adverse effects</subject><subject>Sodium Chloride, Dietary - metabolism</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkMtKAzEUhoMoWi-PUAjiQhejJzOZZLISKd5AUFDBXUiTDE2ZzoxJWulj-SI-k6kt3bo6kP87l3wIDQlcEiDs6hUIhYzxgp0LfgEEcpGVO2hAKKdZSfnHLhpskQN0GMIUACiDch_tC0IFE3yAPl66ZjnrfD9xYRZwV-Of70wZM9euxao1OKgm4mDb4KJbuLjE6b1X0dk2Bvzl4gTbkOLoVIMny976uGK79hjt1aoJ9mRTj9D73e3b6CF7er5_HN08ZZoSFrOcWVVUeTpHV6bmKjdQa8P5uICyLCtrwOZajQurc1FUtakEHbOKsYoWnALPiyN0up7b--5zbkOU027u27RSEiGApQ-LBJVrSPsuBG9r2Xs3U34pCciVTflnU65UScHln01Zpr7hZvh8PLNm27XRl_KzTa6CVk3tVatd2GI5Y1AATdj1GrNJxMJZL4NOArU1zlsdpencP4f8AjFlkmA</recordid><startdate>19970510</startdate><enddate>19970510</enddate><creator>Cusi, Daniele</creator><creator>Barlassina, Cristina</creator><creator>Azzani, Tiziana</creator><creator>Casari, Girgio</creator><creator>Citterio, Lorena</creator><creator>Devoto, Marcella</creator><creator>Glorioso, Nicola</creator><creator>Lanzani, Chiara</creator><creator>Manunta, Paolo</creator><creator>Righetti, Marco</creator><creator>Rivera, Rodolfo</creator><creator>Stella, Paola</creator><creator>Troffa, Chiara</creator><creator>Zagato, Laura</creator><creator>Bianchi, Giuseppe</creator><general>Elsevier Ltd</general><general>Lancet</general><general>Elsevier Limited</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>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope></search><sort><creationdate>19970510</creationdate><title>Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension</title><author>Cusi, Daniele ; Barlassina, Cristina ; Azzani, Tiziana ; Casari, Girgio ; Citterio, Lorena ; Devoto, Marcella ; Glorioso, Nicola ; Lanzani, Chiara ; Manunta, Paolo ; Righetti, Marco ; Rivera, Rodolfo ; Stella, Paola ; Troffa, Chiara ; Zagato, Laura ; Bianchi, Giuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-26ea382149c8df7a2d0fcd77b305558ed0e2cab3ec2938fd894b6866843740723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Aged</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Blood and lymphatic vessels</topic><topic>Calmodulin-Binding Proteins - genetics</topic><topic>Cardiology. Vascular system</topic><topic>Case-Control Studies</topic><topic>Chromosome Mapping</topic><topic>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</topic><topic>France</topic><topic>Gene Frequency</topic><topic>Genes</topic><topic>Genetic Carrier Screening</topic><topic>Genetic Markers</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypertension - genetics</topic><topic>Hypertension - metabolism</topic><topic>Ion transport</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Polymorphism, Genetic</topic><topic>Proteins</topic><topic>Salts</topic><topic>Sodium</topic><topic>Sodium Chloride, Dietary - adverse effects</topic><topic>Sodium Chloride, Dietary - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cusi, Daniele</creatorcontrib><creatorcontrib>Barlassina, Cristina</creatorcontrib><creatorcontrib>Azzani, Tiziana</creatorcontrib><creatorcontrib>Casari, Girgio</creatorcontrib><creatorcontrib>Citterio, Lorena</creatorcontrib><creatorcontrib>Devoto, 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Chiara</au><au>Zagato, Laura</au><au>Bianchi, Giuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>1997-05-10</date><risdate>1997</risdate><volume>349</volume><issue>9062</issue><spage>1353</spage><epage>1357</epage><pages>1353-1357</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an α/β heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an α-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations.
Linkage analysis of three DNA markers at different distances from the α-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the α-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp α-adducin allele.
Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9·1%, 6·5%, and 4·7%) and the significance level for linkage (p=0·0006, p=0·0119, and p=0·0211) both decreased with increasing distance from the α-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p=0·0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15·9 [SE 2·0] vs 7·4 [1·3] mm Hg; p=0·001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14·7 [2·2] vs 6·8 [1·4] mm Hg; p=0·002).
Our findings of significant linkage of the α-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that α-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the α-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>9149697</pmid><doi>10.1016/S0140-6736(97)01029-5</doi><tpages>5</tpages></addata></record> |
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| ispartof | The Lancet (British edition), 1997-05, Vol.349 (9062), p.1353-1357 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_journals_199064609 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete; EBSCOhost Business Source Complete; ProQuest Central UK/Ireland |
| subjects | Aged Arterial hypertension. Arterial hypotension Biological and medical sciences Blood Blood and lymphatic vessels Calmodulin-Binding Proteins - genetics Cardiology. Vascular system Case-Control Studies Chromosome Mapping Clinical manifestations. Epidemiology. Investigative techniques. Etiology France Gene Frequency Genes Genetic Carrier Screening Genetic Markers Humans Hypertension Hypertension - genetics Hypertension - metabolism Ion transport Medical sciences Middle Aged Mutation Mutation - genetics Polymorphism, Genetic Proteins Salts Sodium Sodium Chloride, Dietary - adverse effects Sodium Chloride, Dietary - metabolism |
| title | Polymorphisms of α-adducin and salt sensitivity in patients with essential hypertension |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T14%3A01%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Polymorphisms%20of%20%CE%B1-adducin%20and%20salt%20sensitivity%20in%20patients%20with%20essential%20hypertension&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Cusi,%20Daniele&rft.date=1997-05-10&rft.volume=349&rft.issue=9062&rft.spage=1353&rft.epage=1357&rft.pages=1353-1357&rft.issn=0140-6736&rft.eissn=1474-547X&rft.coden=LANCAO&rft_id=info:doi/10.1016/S0140-6736(97)01029-5&rft_dat=%3Cproquest_cross%3E11712121%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=199064609&rft_id=info:pmid/9149697&rft_els_id=S0140673697010295&rfr_iscdi=true |