{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:28:21Z","timestamp":1789424901381,"version":"build-2803163510"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2000,9]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Gitelman\u2019s syndrome is  an autosomal recessive disorder characterized by electrolyte  disturbances and low blood pressure. The disease is caused by  homozygous or compound heterozygous inactivating mutations in the  thiazide-sensitive NaCl-cotransporter gene leading to reduced renal  sodium reabsorption. We report 4 patients with Gitelman\u2019s syndrome  from southern Sweden, all in whom we identified compound heterozygous  mutations in the thiazide-sensitive NaCl-cotransporter gene (Gly439Ser,  Gly731Arg, Gly741Arg, Thr304Pro, and 2745insAGCA), of which the latter  2 have not been described before. We hypothesized that such mutations  in their heterozygous form protect against primary hypertension in the  general population and that the gene may also harbor activating  mutations that increase the risk for primary hypertension. Accordingly,  the gene was screened for mutations in 20 patients with primary  hypertension and in 20 normotensive subjects by single-strand  conformation polymorphism and direct DNA sequencing. The Arg904Gln,  Gly264Ala, and C1420T variants, found in the mutation screening of  subjects without Gitelman\u2019s syndrome, were studied further. Population  genotype frequencies were determined in 292 unrelated patients  with primary hypertension and 264 unrelated normotensive subjects from  southern Sweden. Gln904 homozygotes were overrepresented in  hypertensive patients compared with normotensive subjects (5 of 292  versus 0 of 264;\n            <jats:italic>P<\/jats:italic>\n            =0.03). In conclusion, we confirm that  Gitelman\u2019s syndrome is caused by mutations in the thiazide-sensitive  NaCl-cotransporter gene. Our results further suggest that subjects  homozygous for the Gln904 variant have an increased risk for  development of primary hypertension.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.36.3.389","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"389-394","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["Genetic Variants of Thiazide-Sensitive NaCl-Cotransporter in Gitelman\u2019s Syndrome and Primary Hypertension"],"prefix":"10.1161","volume":"36","author":[{"given":"Olle","family":"Melander","sequence":"first","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marju","family":"Orho-Melander","sequence":"additional","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Lindblad","sequence":"additional","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart","family":"Ra\u030astam","sequence":"additional","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Groop","sequence":"additional","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U. Lennart","family":"Hulthe\u0301n","sequence":"additional","affiliation":[{"name":"From the Department of Endocrinology (O.M., M.O.M., L.G., U.L.H.) and the  Department of Community Medicine (K.B., U.L., L.R.), Lund University,  Malmo\u0308, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199303000-00002"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90250-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-394"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/355262a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1096-152"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-183"},{"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":"10.1038\/ng1097-171"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0396-248"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5699"},{"key":"e_1_3_2_11_2","first-page":"221","volume":"79","year":"1966","unstructured":"Gitelman HJ, Graham JB, Welt LG. 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