A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension
OBJECTIVETo determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension. METHODSHypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of...
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creator | Rayner, Brian L Owen, E Patricia King, Judy A Soule, Steven G Vreede, Heleen Opie, Lionel H Marais, David Davidson, James S |
description | OBJECTIVETo determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension.
METHODSHypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced.
RESULTSA previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia.
CONCLUSIONSR563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype. |
doi_str_mv | 10.1097/00004872-200305000-00016 |
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METHODSHypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced.
RESULTSA previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia.
CONCLUSIONSR563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype.</description><identifier>ISSN: 0263-6352</identifier><identifier>EISSN: 1473-5598</identifier><identifier>DOI: 10.1097/00004872-200305000-00016</identifier><identifier>PMID: 12714866</identifier><language>eng</language><publisher>England: Lippincott Williams & Wilkins, Inc</publisher><subject>Adult ; African Continental Ancestry Group - ethnology ; African Continental Ancestry Group - genetics ; Aged ; Aldosterone - blood ; Aldosterone - genetics ; Amino Acid Sequence ; Biomarkers - blood ; Female ; Genetic Predisposition to Disease - genetics ; Heart Failure - etiology ; Heterozygote ; Humans ; Hypertension - blood ; Hypertension - complications ; Hypertension - genetics ; Hypokalemia - blood ; Hypokalemia - genetics ; Kidney Failure, Chronic - etiology ; Male ; Middle Aged ; Point Mutation - genetics ; Polymerase Chain Reaction ; Renin - blood ; Renin - genetics ; Severity of Illness Index ; Sodium Channels - genetics ; Sodium Channels - metabolism ; South Africa - ethnology</subject><ispartof>Journal of hypertension, 2003-05, Vol.21 (5), p.921-926</ispartof><rights>2003 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3566-4b4f7d757dcb8c93a9cd97f0cb1d2c242e30927c40e6f477f30bf9cdb97a70413</citedby><cites>FETCH-LOGICAL-c3566-4b4f7d757dcb8c93a9cd97f0cb1d2c242e30927c40e6f477f30bf9cdb97a70413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12714866$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rayner, Brian L</creatorcontrib><creatorcontrib>Owen, E Patricia</creatorcontrib><creatorcontrib>King, Judy A</creatorcontrib><creatorcontrib>Soule, Steven G</creatorcontrib><creatorcontrib>Vreede, Heleen</creatorcontrib><creatorcontrib>Opie, Lionel H</creatorcontrib><creatorcontrib>Marais, David</creatorcontrib><creatorcontrib>Davidson, James S</creatorcontrib><title>A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension</title><title>Journal of hypertension</title><addtitle>J Hypertens</addtitle><description>OBJECTIVETo determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension.
METHODSHypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced.
RESULTSA previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia.
CONCLUSIONSR563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype.</description><subject>Adult</subject><subject>African Continental Ancestry Group - ethnology</subject><subject>African Continental Ancestry Group - genetics</subject><subject>Aged</subject><subject>Aldosterone - blood</subject><subject>Aldosterone - genetics</subject><subject>Amino Acid Sequence</subject><subject>Biomarkers - blood</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Heart Failure - etiology</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Hypertension - blood</subject><subject>Hypertension - complications</subject><subject>Hypertension - genetics</subject><subject>Hypokalemia - blood</subject><subject>Hypokalemia - genetics</subject><subject>Kidney Failure, Chronic - etiology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Point Mutation - genetics</subject><subject>Polymerase Chain Reaction</subject><subject>Renin - blood</subject><subject>Renin - genetics</subject><subject>Severity of Illness Index</subject><subject>Sodium Channels - genetics</subject><subject>Sodium Channels - metabolism</subject><subject>South Africa - ethnology</subject><issn>0263-6352</issn><issn>1473-5598</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcuKFTEQQIMoznX0FyQrV9OaVyed5TD4ggFRdB3S6Wo6mk6uSZpm1v64Ge8dXRkIVQmnqqAOQpiS15Ro9Ya0IwbFOkYIJ317de1S-QgdqFC863s9PEYHwiTvJO_ZBXpWyveGDFrxp-iCMkXFIOUB_brGEXa8btVWn-IV_tJL_vkKpxnXBfAI1eKyjVv09eEPjr6F4G3AJU1-W7FbbIwQsC0lOW8rTHhvDA5p7zJE39repzZMqVTIKQJe7o6QK8TShj5HT2YbCrw4x0v07d3brzcfuttP7z_eXN92jvdSdmIUs5pUryY3Dk5zq92k1UzcSCfmmGDAiWbKCQJyFkrNnIxzY0atrCKC8kv06tT3mNPPDUo1qy8OQrAR0laM4oxTrlkDhxPociolw2yO2a823xlKzL0A8yDA_BVg_ghopS_PM7Zxhelf4XnjDRAnYE-h7aL8CNsO2SxgQ13M_8Ty3xZGkcE</recordid><startdate>200305</startdate><enddate>200305</enddate><creator>Rayner, Brian L</creator><creator>Owen, E Patricia</creator><creator>King, Judy A</creator><creator>Soule, Steven G</creator><creator>Vreede, Heleen</creator><creator>Opie, Lionel H</creator><creator>Marais, David</creator><creator>Davidson, James S</creator><general>Lippincott Williams & Wilkins, Inc</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>200305</creationdate><title>A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension</title><author>Rayner, Brian L ; Owen, E Patricia ; King, Judy A ; Soule, Steven G ; Vreede, Heleen ; Opie, Lionel H ; Marais, David ; Davidson, James S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3566-4b4f7d757dcb8c93a9cd97f0cb1d2c242e30927c40e6f477f30bf9cdb97a70413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>African Continental Ancestry Group - ethnology</topic><topic>African Continental Ancestry Group - genetics</topic><topic>Aged</topic><topic>Aldosterone - blood</topic><topic>Aldosterone - genetics</topic><topic>Amino Acid Sequence</topic><topic>Biomarkers - blood</topic><topic>Female</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Heart Failure - etiology</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Hypertension - blood</topic><topic>Hypertension - complications</topic><topic>Hypertension - genetics</topic><topic>Hypokalemia - blood</topic><topic>Hypokalemia - genetics</topic><topic>Kidney Failure, Chronic - etiology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Point Mutation - genetics</topic><topic>Polymerase Chain Reaction</topic><topic>Renin - blood</topic><topic>Renin - genetics</topic><topic>Severity of Illness Index</topic><topic>Sodium Channels - genetics</topic><topic>Sodium Channels - metabolism</topic><topic>South Africa - ethnology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rayner, Brian L</creatorcontrib><creatorcontrib>Owen, E Patricia</creatorcontrib><creatorcontrib>King, Judy A</creatorcontrib><creatorcontrib>Soule, Steven G</creatorcontrib><creatorcontrib>Vreede, Heleen</creatorcontrib><creatorcontrib>Opie, Lionel H</creatorcontrib><creatorcontrib>Marais, David</creatorcontrib><creatorcontrib>Davidson, James S</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>Journal of hypertension</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rayner, Brian L</au><au>Owen, E Patricia</au><au>King, Judy A</au><au>Soule, Steven G</au><au>Vreede, Heleen</au><au>Opie, Lionel H</au><au>Marais, David</au><au>Davidson, James S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension</atitle><jtitle>Journal of hypertension</jtitle><addtitle>J Hypertens</addtitle><date>2003-05</date><risdate>2003</risdate><volume>21</volume><issue>5</issue><spage>921</spage><epage>926</epage><pages>921-926</pages><issn>0263-6352</issn><eissn>1473-5598</eissn><abstract>OBJECTIVETo determine the relationship between R563Q, a mutation of the renal epithelial sodium channel, and hypertension.
METHODSHypertensive patients with low renin and aldosterone, hypokalemia or resistant hypertension were selected for DNA analysis. Genomic DNA encoding the C-terminal domain of the epithelial sodium channel beta subunit from hypertensives and controls was amplified by polymerase chain reaction and screened for the R563Q mutation by digestion with Sfc1 restriction enzyme, or sequenced.
RESULTSA previously undescribed mutation, R563Q, of the beta epithelial sodium channel was found in 10 of 139 black hypertensives, but was not present in any of 103 black normotensives, a significant (P = 0.0058) difference in frequency. The frequency of the mutation in the subgroup of black low-renin, low-aldosterone hypertensives (four of 14) was significantly (P = 0.0001) greater than in normotensives, and was also greater (P = 0.041) than in normal-high renin hypertensives, suggesting that R563Q is an activating mutation of the epithelial sodium channel. R563Q was also found in seven out of 250 mixed ancestry hypertensives, and was significantly (P = 0.017) associated with low-renin, low-aldosterone hypertension in this population group. The mutation was found in one of 100 mixed ancestry normotensives but not in any of 136 white hypertensives. Of the 18 R563Q patients, 11 had severe hypertension, leading to renal failure in two cases, while only two had hypokalaemia.
CONCLUSIONSR563Q, a new variant of the beta epithelial sodium channel, is associated with low-renin, low-aldosterone hypertension, in South African black and mixed-ancestry patients. Only a minority of individuals with the R563Q allelle fully express the Liddle's syndrome phenotype.</abstract><cop>England</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>12714866</pmid><doi>10.1097/00004872-200305000-00016</doi><tpages>6</tpages></addata></record> |
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subjects | Adult African Continental Ancestry Group - ethnology African Continental Ancestry Group - genetics Aged Aldosterone - blood Aldosterone - genetics Amino Acid Sequence Biomarkers - blood Female Genetic Predisposition to Disease - genetics Heart Failure - etiology Heterozygote Humans Hypertension - blood Hypertension - complications Hypertension - genetics Hypokalemia - blood Hypokalemia - genetics Kidney Failure, Chronic - etiology Male Middle Aged Point Mutation - genetics Polymerase Chain Reaction Renin - blood Renin - genetics Severity of Illness Index Sodium Channels - genetics Sodium Channels - metabolism South Africa - ethnology |
title | A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension |
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