Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study
There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analy...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1998-05, Vol.97 (18), p.1766-1772 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | O'DONNELL, C. J LINDPAINTNER, K LARSON, M. G RAO, V. S ORDOVAS, J. M SCHAEFER, E. J MYERS, R. H LEVY, D |
| description | There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses.
The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women.
In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted. |
| doi_str_mv | 10.1161/01.CIR.97.18.1766 |
| format | Article |
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The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women.
In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.97.18.1766</identifier><identifier>PMID: 9603529</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Aged ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Pressure - genetics ; Cardiology. Vascular system ; Cardiovascular Diseases - epidemiology ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Cohort Studies ; Female ; Genetic Linkage ; Genotype ; Human Growth Hormone - genetics ; Humans ; Hypertension - epidemiology ; Hypertension - genetics ; Hypertension - physiopathology ; Linear Models ; Male ; Medical sciences ; Microsatellite Repeats ; Middle Aged ; Odds Ratio ; Peptidyl-Dipeptidase A - genetics ; Polymorphism, Genetic ; Prospective Studies ; Quantitative Trait, Heritable ; Risk Factors ; Sex Characteristics ; United States - epidemiology</subject><ispartof>Circulation (New York, N.Y.), 1998-05, Vol.97 (18), p.1766-1772</ispartof><rights>1998 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. May 12, 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-636a728ac61eac7cc6ffcb0629fbfb0c5dd062544456838791edf259443c1baf3</citedby><cites>FETCH-LOGICAL-c485t-636a728ac61eac7cc6ffcb0629fbfb0c5dd062544456838791edf259443c1baf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2229213$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9603529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>O'DONNELL, C. J</creatorcontrib><creatorcontrib>LINDPAINTNER, K</creatorcontrib><creatorcontrib>LARSON, M. G</creatorcontrib><creatorcontrib>RAO, V. S</creatorcontrib><creatorcontrib>ORDOVAS, J. M</creatorcontrib><creatorcontrib>SCHAEFER, E. J</creatorcontrib><creatorcontrib>MYERS, R. H</creatorcontrib><creatorcontrib>LEVY, D</creatorcontrib><title>Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses.
The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women.
In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.</description><subject>Adult</subject><subject>Aged</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Pressure - genetics</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Genetic Linkage</subject><subject>Genotype</subject><subject>Human Growth Hormone - genetics</subject><subject>Humans</subject><subject>Hypertension - epidemiology</subject><subject>Hypertension - genetics</subject><subject>Hypertension - physiopathology</subject><subject>Linear Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Peptidyl-Dipeptidase A - genetics</subject><subject>Polymorphism, Genetic</subject><subject>Prospective Studies</subject><subject>Quantitative Trait, Heritable</subject><subject>Risk Factors</subject><subject>Sex Characteristics</subject><subject>United States - epidemiology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1q3DAUhUVpSKdpH6CLgiilO7uSbMnWsgxJEwgE-rMWsnw1o9SWppKcMH2pvmJlMmTR1eXc890jwUHoHSU1pYJ-JrTe3nyrZVfTvqadEC_QhnLWVi1v5Eu0IYTIqmsYe4Vep3RfpGg6fo7OpSANZ3KD_l4-uBG8AWxDxDqlYJzOLnis_Yh34CE7gyfnf-kd4GBx3kOxdi5k8Mn5ygT_ADE7v8Pg_xxnwFMwS8KPLu_x_ngo3gqeAocphBEfIqS0RMDO4xk8HpaMfcj4MayqLNdHrqKeS-pez_gadMz4e17G4xt0ZvWU4O1pXqCfV5c_ttfV7d3Xm-2X28q0Pc-VaITuWK-NoKBNZ4yw1gxEMGkHOxDDx7EI3rYtF33Td5LCaBmXbdsYOmjbXKBPT7mHGH4vkLKaXTIwTdpDWJLqZC8JI20BP_wH3ocl-vI3xSgTXFBOC0SfIBNDShGsOkQ363hUlKi1SUWoKk0q2Snaq7XJcvP-FLwMM4zPF6fqiv_x5Otk9GSj9salZ4wxJhltmn98uan4</recordid><startdate>19980512</startdate><enddate>19980512</enddate><creator>O'DONNELL, C. J</creator><creator>LINDPAINTNER, K</creator><creator>LARSON, M. G</creator><creator>RAO, V. S</creator><creator>ORDOVAS, J. M</creator><creator>SCHAEFER, E. J</creator><creator>MYERS, R. H</creator><creator>LEVY, D</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19980512</creationdate><title>Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study</title><author>O'DONNELL, C. J ; LINDPAINTNER, K ; LARSON, M. G ; RAO, V. S ; ORDOVAS, J. M ; SCHAEFER, E. J ; MYERS, R. 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S</creatorcontrib><creatorcontrib>ORDOVAS, J. M</creatorcontrib><creatorcontrib>SCHAEFER, E. J</creatorcontrib><creatorcontrib>MYERS, R. H</creatorcontrib><creatorcontrib>LEVY, D</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 Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>O'DONNELL, C. J</au><au>LINDPAINTNER, K</au><au>LARSON, M. G</au><au>RAO, V. S</au><au>ORDOVAS, J. M</au><au>SCHAEFER, E. J</au><au>MYERS, R. H</au><au>LEVY, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1998-05-12</date><risdate>1998</risdate><volume>97</volume><issue>18</issue><spage>1766</spage><epage>1772</epage><pages>1766-1772</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses.
The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women.
In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>9603529</pmid><doi>10.1161/01.CIR.97.18.1766</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; EZB-FREE-00999 freely available EZB journals; Journals@Ovid Complete |
| subjects | Adult Aged Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Blood Pressure - genetics Cardiology. Vascular system Cardiovascular Diseases - epidemiology Clinical manifestations. Epidemiology. Investigative techniques. Etiology Cohort Studies Female Genetic Linkage Genotype Human Growth Hormone - genetics Humans Hypertension - epidemiology Hypertension - genetics Hypertension - physiopathology Linear Models Male Medical sciences Microsatellite Repeats Middle Aged Odds Ratio Peptidyl-Dipeptidase A - genetics Polymorphism, Genetic Prospective Studies Quantitative Trait, Heritable Risk Factors Sex Characteristics United States - epidemiology |
| title | Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study |
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