Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake
Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocort...
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| Veröffentlicht in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2016-02, Vol.67 (2), p.342-348 |
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| creator | Lanzani, Chiara Gatti, Guido Citterio, Lorena Messaggio, Elisabetta Delli Carpini, Simona Simonini, Marco Casamassima, Nunzia Zagato, Laura Brioni, Elena Hamlyn, John M Manunta, Paolo |
| description | Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake ( |
| doi_str_mv | 10.1161/HYPERTENSIONAHA.115.06415 |
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Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake (<100 mEq/d, 2 weeks) among patients with mild essential hypertension. During the low salt diet, the declines in both systolic BP (SBP: -8.7±1.7 versus -3.0±1.5; P=0.013) and diastolic BP (DBP: -5.1±0.98 versus -1.4±0.94 mm Hg; P<0.05), and the slope of the long-term pressure-natriuresis relationship affected significantly the presence of the lanosterol synthase rs2254524 A variant (AA: 0.71±0.22, AC 0.09±0.13, and CC 0.04±0.11 mEq/mm Hg/24 h; P=0.028). In addition, BP rose in ≈25% of the patients in response to the low salt diet and this was associated with increased circulating EO. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects, that is, increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.115.06415</identifier><identifier>PMID: 26667413</identifier><language>eng</language><publisher>United States</publisher><subject>Adolescent ; Adult ; Aged ; Blood Pressure - drug effects ; Blood Pressure - physiology ; Diet, Sodium-Restricted ; Enzyme Inhibitors - pharmacokinetics ; Female ; Genotype ; Humans ; Hypertension - genetics ; Hypertension - metabolism ; Hypertension - therapy ; Intramolecular Transferases - genetics ; Intramolecular Transferases - metabolism ; Male ; Middle Aged ; Ouabain - pharmacokinetics ; Polymorphism, Genetic ; RNA - genetics ; Young Adult</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2016-02, Vol.67 (2), p.342-348</ispartof><rights>2015 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-add270a7c6c9bd3337f7539cca7a8e50e8a1376e0d37f6a67940f1e5afd613b53</citedby><cites>FETCH-LOGICAL-c423t-add270a7c6c9bd3337f7539cca7a8e50e8a1376e0d37f6a67940f1e5afd613b53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3674,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26667413$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lanzani, Chiara</creatorcontrib><creatorcontrib>Gatti, Guido</creatorcontrib><creatorcontrib>Citterio, Lorena</creatorcontrib><creatorcontrib>Messaggio, Elisabetta</creatorcontrib><creatorcontrib>Delli Carpini, Simona</creatorcontrib><creatorcontrib>Simonini, Marco</creatorcontrib><creatorcontrib>Casamassima, Nunzia</creatorcontrib><creatorcontrib>Zagato, Laura</creatorcontrib><creatorcontrib>Brioni, Elena</creatorcontrib><creatorcontrib>Hamlyn, John M</creatorcontrib><creatorcontrib>Manunta, Paolo</creatorcontrib><title>Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake (<100 mEq/d, 2 weeks) among patients with mild essential hypertension. During the low salt diet, the declines in both systolic BP (SBP: -8.7±1.7 versus -3.0±1.5; P=0.013) and diastolic BP (DBP: -5.1±0.98 versus -1.4±0.94 mm Hg; P<0.05), and the slope of the long-term pressure-natriuresis relationship affected significantly the presence of the lanosterol synthase rs2254524 A variant (AA: 0.71±0.22, AC 0.09±0.13, and CC 0.04±0.11 mEq/mm Hg/24 h; P=0.028). In addition, BP rose in ≈25% of the patients in response to the low salt diet and this was associated with increased circulating EO. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects, that is, increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Blood Pressure - drug effects</subject><subject>Blood Pressure - physiology</subject><subject>Diet, Sodium-Restricted</subject><subject>Enzyme Inhibitors - pharmacokinetics</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hypertension - genetics</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - therapy</subject><subject>Intramolecular Transferases - genetics</subject><subject>Intramolecular Transferases - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Ouabain - pharmacokinetics</subject><subject>Polymorphism, Genetic</subject><subject>RNA - genetics</subject><subject>Young Adult</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUV1r20AQPEpL4yT9C-X61held7ov66VgjBsbTBziFNqnY61bWWqlO1cnJfjf59qkoQ0sLMzMzu4yhHzg7IJzzT8tv18vbm4XV9vV5mq2nCVQXTAtuXpFJlzlMpNKi9dkwnghs4LzbyfkNMYfjHEppXlLTnKttZFcTEi3Bh_igH1o6fbohxoi0kv0SK9De-xCf6ib2EUK3tF5DX6PkTaeLrwLe_RhjHQzwg4SlGqokd5gPASfTIZA1-GeboNrxo6u_AA_8Zy8qaCN-O6pn5GvXxa382W23lyu5rN1VspcDBk4lxsGptRlsXNCCFMZJYqyBANTVAynwIXRyFxiNGhTSFZxVFA5zcVOiTPy-dH3MO46dCX6oYfWHvqmg_5oAzT2f8Y3td2HOysNFyLXyeDjk0Effo0YB9s1scS2BY_pacuNZlNVFNokafEoLfsQY4_V8xrO7O-47Iu4Eqjsn7jS7Pt_73ye_JuPeABP_ZXq</recordid><startdate>20160201</startdate><enddate>20160201</enddate><creator>Lanzani, Chiara</creator><creator>Gatti, Guido</creator><creator>Citterio, Lorena</creator><creator>Messaggio, Elisabetta</creator><creator>Delli Carpini, Simona</creator><creator>Simonini, Marco</creator><creator>Casamassima, Nunzia</creator><creator>Zagato, Laura</creator><creator>Brioni, Elena</creator><creator>Hamlyn, John M</creator><creator>Manunta, Paolo</creator><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><scope>5PM</scope></search><sort><creationdate>20160201</creationdate><title>Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake</title><author>Lanzani, Chiara ; Gatti, Guido ; Citterio, Lorena ; Messaggio, Elisabetta ; Delli Carpini, Simona ; Simonini, Marco ; Casamassima, Nunzia ; Zagato, Laura ; Brioni, Elena ; Hamlyn, John M ; Manunta, Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-add270a7c6c9bd3337f7539cca7a8e50e8a1376e0d37f6a67940f1e5afd613b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Blood Pressure - drug effects</topic><topic>Blood Pressure - physiology</topic><topic>Diet, Sodium-Restricted</topic><topic>Enzyme Inhibitors - pharmacokinetics</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hypertension - genetics</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - therapy</topic><topic>Intramolecular Transferases - genetics</topic><topic>Intramolecular Transferases - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Ouabain - pharmacokinetics</topic><topic>Polymorphism, Genetic</topic><topic>RNA - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lanzani, Chiara</creatorcontrib><creatorcontrib>Gatti, Guido</creatorcontrib><creatorcontrib>Citterio, Lorena</creatorcontrib><creatorcontrib>Messaggio, Elisabetta</creatorcontrib><creatorcontrib>Delli Carpini, Simona</creatorcontrib><creatorcontrib>Simonini, Marco</creatorcontrib><creatorcontrib>Casamassima, Nunzia</creatorcontrib><creatorcontrib>Zagato, Laura</creatorcontrib><creatorcontrib>Brioni, Elena</creatorcontrib><creatorcontrib>Hamlyn, John M</creatorcontrib><creatorcontrib>Manunta, Paolo</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lanzani, Chiara</au><au>Gatti, Guido</au><au>Citterio, Lorena</au><au>Messaggio, Elisabetta</au><au>Delli Carpini, Simona</au><au>Simonini, Marco</au><au>Casamassima, Nunzia</au><au>Zagato, Laura</au><au>Brioni, Elena</au><au>Hamlyn, John M</au><au>Manunta, Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2016-02-01</date><risdate>2016</risdate><volume>67</volume><issue>2</issue><spage>342</spage><epage>348</epage><pages>342-348</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><abstract>Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake (<100 mEq/d, 2 weeks) among patients with mild essential hypertension. During the low salt diet, the declines in both systolic BP (SBP: -8.7±1.7 versus -3.0±1.5; P=0.013) and diastolic BP (DBP: -5.1±0.98 versus -1.4±0.94 mm Hg; P<0.05), and the slope of the long-term pressure-natriuresis relationship affected significantly the presence of the lanosterol synthase rs2254524 A variant (AA: 0.71±0.22, AC 0.09±0.13, and CC 0.04±0.11 mEq/mm Hg/24 h; P=0.028). In addition, BP rose in ≈25% of the patients in response to the low salt diet and this was associated with increased circulating EO. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects, that is, increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives.</abstract><cop>United States</cop><pmid>26667413</pmid><doi>10.1161/HYPERTENSIONAHA.115.06415</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Hypertension (Dallas, Tex. 1979), 2016-02, Vol.67 (2), p.342-348 |
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| subjects | Adolescent Adult Aged Blood Pressure - drug effects Blood Pressure - physiology Diet, Sodium-Restricted Enzyme Inhibitors - pharmacokinetics Female Genotype Humans Hypertension - genetics Hypertension - metabolism Hypertension - therapy Intramolecular Transferases - genetics Intramolecular Transferases - metabolism Male Middle Aged Ouabain - pharmacokinetics Polymorphism, Genetic RNA - genetics Young Adult |
| title | Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake |
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