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Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter
Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isoca...
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| Published in: | Hypertension (Dallas, Tex. 1979) Tex. 1979), 2012-11, Vol.60 (5), p.1359-1366 |
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| container_end_page | 1366 |
| container_issue | 5 |
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| container_title | Hypertension (Dallas, Tex. 1979) |
| container_volume | 60 |
| creator | Carey, Robert M Schoeffel, Cynthia D Gildea, John J Jones, John E McGrath, Helen E Gordon, Lindsay N Park, Min Jeong Sobota, Rafal S Underwood, Patricia C Williams, Jonathan Sun, Bei Raby, Benjamin Lasky-Su, Jessica Hopkins, Paul N Adler, Gail K Williams, Scott M Jose, Pedro A Felder, Robin A |
| description | Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na (10 mmol/d) and 7 days of high Na (300 mmol/d) intake. Salt sensitivity was defined as a ≥7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P |
| doi_str_mv | 10.1161/HYPERTENSIONAHA.112.196071 |
| format | article |
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We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na (10 mmol/d) and 7 days of high Na (300 mmol/d) intake. Salt sensitivity was defined as a ≥7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0×10 and 3.1×10 with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9×10 and 2.6×10 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2×10]; rs1017783 [P=1.1×10]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/HYPERTENSIONAHA.112.196071</identifier><identifier>PMID: 22987918</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Adult ; Aldosterone - blood ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Pressure - genetics ; Blood Pressure - physiology ; Body Mass Index ; Cardiology. Vascular system ; Clinical manifestations. Epidemiology. Investigative techniques. Etiology ; Diet ; Dose-Response Relationship, Drug ; Female ; Gene Frequency ; Genetic Predisposition to Disease - genetics ; Genotype ; Humans ; Hypertension - etiology ; Hypertension - genetics ; Hypertension - physiopathology ; Logistic Models ; Male ; Medical sciences ; Meta-Analysis as Topic ; Middle Aged ; Odds Ratio ; Outcome Assessment (Health Care) ; Polymorphism, Single Nucleotide ; Renin - blood ; Sodium Chloride, Dietary - administration & dosage ; Sodium Chloride, Dietary - adverse effects ; Sodium-Bicarbonate Symporters - genetics</subject><ispartof>Hypertension (Dallas, Tex. 1979), 2012-11, Vol.60 (5), p.1359-1366</ispartof><rights>2012 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5131-cb365fb7aeba711d34839b4831ab4bdc296d8ecf403fcdb8a0748570ccee762a3</citedby><cites>FETCH-LOGICAL-c5131-cb365fb7aeba711d34839b4831ab4bdc296d8ecf403fcdb8a0748570ccee762a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26494362$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22987918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carey, Robert M</creatorcontrib><creatorcontrib>Schoeffel, Cynthia D</creatorcontrib><creatorcontrib>Gildea, John J</creatorcontrib><creatorcontrib>Jones, John E</creatorcontrib><creatorcontrib>McGrath, Helen E</creatorcontrib><creatorcontrib>Gordon, Lindsay N</creatorcontrib><creatorcontrib>Park, Min Jeong</creatorcontrib><creatorcontrib>Sobota, Rafal S</creatorcontrib><creatorcontrib>Underwood, Patricia C</creatorcontrib><creatorcontrib>Williams, Jonathan</creatorcontrib><creatorcontrib>Sun, Bei</creatorcontrib><creatorcontrib>Raby, Benjamin</creatorcontrib><creatorcontrib>Lasky-Su, Jessica</creatorcontrib><creatorcontrib>Hopkins, Paul N</creatorcontrib><creatorcontrib>Adler, Gail K</creatorcontrib><creatorcontrib>Williams, Scott M</creatorcontrib><creatorcontrib>Jose, Pedro A</creatorcontrib><creatorcontrib>Felder, Robin A</creatorcontrib><title>Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na (10 mmol/d) and 7 days of high Na (300 mmol/d) intake. Salt sensitivity was defined as a ≥7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0×10 and 3.1×10 with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9×10 and 2.6×10 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2×10]; rs1017783 [P=1.1×10]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.</description><subject>Adult</subject><subject>Aldosterone - blood</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>Blood Pressure - physiology</subject><subject>Body Mass Index</subject><subject>Cardiology. Vascular system</subject><subject>Clinical manifestations. Epidemiology. Investigative techniques. Etiology</subject><subject>Diet</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Hypertension - etiology</subject><subject>Hypertension - genetics</subject><subject>Hypertension - physiopathology</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Meta-Analysis as Topic</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Outcome Assessment (Health Care)</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Renin - blood</subject><subject>Sodium Chloride, Dietary - administration & dosage</subject><subject>Sodium Chloride, Dietary - adverse effects</subject><subject>Sodium-Bicarbonate Symporters - genetics</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNkNtKAzEQhoMoWg-vIEHwcjWzmz15IdRSbUFssYp6tSTZLBvdbUpma-nbG6kH8MqbGRi-f5j5CDkBdgaQwPnoZTq8fxjezcaTu_6o74fhGeQJS2GL9CAOecDjJNomPQY5D3KA5z2yj_jKGHDO012yF4Z5luaQ9cjbTDQdnek5ms68m25NbUWvGmtLOnUacek0HSPtI1plRKdL-mS6mk5ts26tW9QGW6RmTrta05ktzbINrowSTtq5p-nAdk7McWFdp90h2alEg_roqx-Qx-vhw2AU3E5uxoP-baBiiCBQMkriSqZCS5EClBHPolz6AkJyWaowT8pMq4qzqFKlzARLeRanTCmt0yQU0QG52OxVziI6XRULZ1rh1gWw4tNg8cegH4bFxqAPH2_Ci6VsdfkT_VbmgdMvQKASTeX_UwZ_uYTnPEpCz11uuJVt_PP41ixX2hW19sLr_1zyAcN_kis</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Carey, Robert M</creator><creator>Schoeffel, Cynthia D</creator><creator>Gildea, John J</creator><creator>Jones, John E</creator><creator>McGrath, Helen E</creator><creator>Gordon, Lindsay N</creator><creator>Park, Min Jeong</creator><creator>Sobota, Rafal S</creator><creator>Underwood, Patricia C</creator><creator>Williams, Jonathan</creator><creator>Sun, Bei</creator><creator>Raby, Benjamin</creator><creator>Lasky-Su, Jessica</creator><creator>Hopkins, Paul N</creator><creator>Adler, Gail K</creator><creator>Williams, Scott M</creator><creator>Jose, Pedro A</creator><creator>Felder, Robin A</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</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></search><sort><creationdate>201211</creationdate><title>Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter</title><author>Carey, Robert M ; Schoeffel, Cynthia D ; Gildea, John J ; Jones, John E ; McGrath, Helen E ; Gordon, Lindsay N ; Park, Min Jeong ; Sobota, Rafal S ; Underwood, Patricia C ; Williams, Jonathan ; Sun, Bei ; Raby, Benjamin ; Lasky-Su, Jessica ; Hopkins, Paul N ; Adler, Gail K ; Williams, Scott M ; Jose, Pedro A ; Felder, Robin A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5131-cb365fb7aeba711d34839b4831ab4bdc296d8ecf403fcdb8a0748570ccee762a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Aldosterone - blood</topic><topic>Arterial hypertension. 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Etiology</topic><topic>Diet</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>Humans</topic><topic>Hypertension - etiology</topic><topic>Hypertension - genetics</topic><topic>Hypertension - physiopathology</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Meta-Analysis as Topic</topic><topic>Middle Aged</topic><topic>Odds Ratio</topic><topic>Outcome Assessment (Health Care)</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Renin - blood</topic><topic>Sodium Chloride, Dietary - administration & dosage</topic><topic>Sodium Chloride, Dietary - adverse effects</topic><topic>Sodium-Bicarbonate Symporters - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carey, Robert M</creatorcontrib><creatorcontrib>Schoeffel, Cynthia D</creatorcontrib><creatorcontrib>Gildea, John J</creatorcontrib><creatorcontrib>Jones, John E</creatorcontrib><creatorcontrib>McGrath, Helen E</creatorcontrib><creatorcontrib>Gordon, Lindsay N</creatorcontrib><creatorcontrib>Park, Min Jeong</creatorcontrib><creatorcontrib>Sobota, Rafal S</creatorcontrib><creatorcontrib>Underwood, Patricia C</creatorcontrib><creatorcontrib>Williams, Jonathan</creatorcontrib><creatorcontrib>Sun, Bei</creatorcontrib><creatorcontrib>Raby, Benjamin</creatorcontrib><creatorcontrib>Lasky-Su, Jessica</creatorcontrib><creatorcontrib>Hopkins, Paul N</creatorcontrib><creatorcontrib>Adler, Gail K</creatorcontrib><creatorcontrib>Williams, Scott M</creatorcontrib><creatorcontrib>Jose, Pedro A</creatorcontrib><creatorcontrib>Felder, Robin A</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><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carey, Robert M</au><au>Schoeffel, Cynthia D</au><au>Gildea, John J</au><au>Jones, John E</au><au>McGrath, Helen E</au><au>Gordon, Lindsay N</au><au>Park, Min Jeong</au><au>Sobota, Rafal S</au><au>Underwood, Patricia C</au><au>Williams, Jonathan</au><au>Sun, Bei</au><au>Raby, Benjamin</au><au>Lasky-Su, Jessica</au><au>Hopkins, Paul N</au><au>Adler, Gail K</au><au>Williams, Scott M</au><au>Jose, Pedro A</au><au>Felder, Robin A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>2012-11</date><risdate>2012</risdate><volume>60</volume><issue>5</issue><spage>1359</spage><epage>1366</epage><pages>1359-1366</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na (10 mmol/d) and 7 days of high Na (300 mmol/d) intake. Salt sensitivity was defined as a ≥7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0×10 and 3.1×10 with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9×10 and 2.6×10 and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2×10]; rs1017783 [P=1.1×10]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>22987918</pmid><doi>10.1161/HYPERTENSIONAHA.112.196071</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0194-911X |
| ispartof | Hypertension (Dallas, Tex. 1979), 2012-11, Vol.60 (5), p.1359-1366 |
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| language | eng |
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| source | EZB Electronic Journals Library |
| subjects | Adult Aldosterone - blood Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Blood Pressure - genetics Blood Pressure - physiology Body Mass Index Cardiology. Vascular system Clinical manifestations. Epidemiology. Investigative techniques. Etiology Diet Dose-Response Relationship, Drug Female Gene Frequency Genetic Predisposition to Disease - genetics Genotype Humans Hypertension - etiology Hypertension - genetics Hypertension - physiopathology Logistic Models Male Medical sciences Meta-Analysis as Topic Middle Aged Odds Ratio Outcome Assessment (Health Care) Polymorphism, Single Nucleotide Renin - blood Sodium Chloride, Dietary - administration & dosage Sodium Chloride, Dietary - adverse effects Sodium-Bicarbonate Symporters - genetics |
| title | Salt Sensitivity of Blood Pressure Is Associated With Polymorphisms in the Sodium-Bicarbonate Cotransporter |
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