{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:37:25Z","timestamp":1783463845476,"version":"3.55.0"},"reference-count":12,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,6]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The  relationship between salt homeostasis and blood pressure has remained  difficult to establish from epidemiological studies of the general  population. Recently, mendelian forms of hypertension have demonstrated  that mutations that increase renal salt balance lead to higher blood  pressure, suggesting that mutations that decrease the net salt balance  might have the converse effect. Gitelman\u2019s syndrome, caused by loss of  function mutations in the Na-Cl cotransporter of the distal convoluted  tubule (\n            <jats:italic>NCCT<\/jats:italic>\n            ), features  inherited hypokalemic alkalosis with so-called \u201cnormal\u201d blood  pressure. We hypothesized that the mild salt wasting of Gitelman\u2019s  syndrome results in reduced blood pressure and protection from  hypertension. We have formally addressed this question through the  study of 199 members of a large Amish kindred with Gitelman\u2019s  syndrome. Through genetic testing, family members were identified as  inheriting 0 (n=60), 1 (n=113), or 2 (n=26) mutations in\n            <jats:italic>NCCT<\/jats:italic>\n            , permitting an unbiased  assessment of the clinical consequences of inheriting these mutations  by comparison of the phenotypes of relatives with contrasting  genotypes. The results demonstrate high penetrance of  hypokalemic alkalosis, hypomagnesemia, and hypocalciuria in patients  inheriting 2 mutant\n            <jats:italic>NCCT<\/jats:italic>\n            alleles. In addition, the\n            <jats:italic>NCCT<\/jats:italic>\n            genotype was a  significant predictor of blood pressure, with homozygous mutant family  members having significantly lower age- and gender-adjusted  systolic and diastolic blood pressures than those  of their wild-type relatives. Moreover, both homozygote and  heterozygote subjects had significantly higher 24-hour urinary  Na\n            <jats:sup>+<\/jats:sup>\n            than did wild-type subjects, reflecting  a self-selected higher salt intake. Finally, heterozygous children, but  not adults, had significantly lower blood pressures than those of the  wild-type relatives. These findings provide formal demonstration that  inherited mutations that impair renal salt handling lower blood  pressure in humans.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.37.6.1458","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"1458-1464","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":140,"title":["Mutations in the Na-Cl Cotransporter Reduce Blood Pressure in Humans"],"prefix":"10.1161","volume":"37","author":[{"given":"Dinna N.","family":"Cruz","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Simon","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Nelson-Williams","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Farhi","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Finberg","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Burleson","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Gill","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Lifton","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (D.N.C., D.B.S., R.P.L.) and Genetics  (C.N.-W., A.F., K.F., L.B., R.P.L.), Howard Hughes Medical Institute, Yale  University School of Medicine, New Haven, Conn; and the National Institutes of  Health (J.R.G.), Bethesda, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0033-0620(99)70007-1"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5262.676"},{"key":"e_1_3_2_3_2","first-page":"61","volume":"11","year":"1998","unstructured":"Bettinelli A, Vezzoli G, Colussi G, Bianchetti MG, Sereni F, Casari G. 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Neth J Med. 1991;39:148\u2013152.","journal-title":"Neth J Med"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000185159"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199801000-00008"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-24"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.9.5759"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.7.2749"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32499-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5424.103"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2063193"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.37.6.1458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T18:37:00Z","timestamp":1715539020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.37.6.1458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6]]},"references-count":12,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,6]]}},"alternative-id":["10.1161\/01.HYP.37.6.1458"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.37.6.1458","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6]]},"assertion":[{"value":"2000-09-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}