Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1
ObjectivesHuman urate transporter 1 (URAT1) is a member of the organic anion transporter family (SLC22A12) that primarily regulates the renal tubular reabsorption of uric acid. This case–control study was designed to analyse whether hURAT1 might also be a candidate gene for hyperuricaemia or hypouri...
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| description | ObjectivesHuman urate transporter 1 (URAT1) is a member of the organic anion transporter family (SLC22A12) that primarily regulates the renal tubular reabsorption of uric acid. This case–control study was designed to analyse whether hURAT1 might also be a candidate gene for hyperuricaemia or hypouricaemia.SettingWe recruited 68 healthy volunteers and divided them into two groups: a normal uric acid group and a hyperuricaemia group. We analysed the sequence of the URAT1 gene and found five significant single nucleotide polymorphisms (SNPs). We then selected 900 male subjects from the 262 200 enrolled in the Korean Cancer Prevention Study-II (KCPS-II) cohort for further genetic analysis.ParticipantsDNA samples from 36 individuals with normal uric acid (8.5 mg/dL) were sequenced. Five significant SNPs (rs7929627, rs75786299, rs3825017, rs11602903 and rs121907892) were identified. We then chose 900 subjects from the KCPS-II cohort consisting of 450 subjects with normal uric acid (UA 8.7 mg/dL). The groups were matched by age, body mass index, metabolic syndrome and use of anti-hypertensive medication.Primary outcome measuresWe compared the OR of the incidence of hyperuricaemia by URAT1 genotype.ResultsThe strongest association with hyperuricaemia was observed for rs75786299 (IVS3+11A/G) with an OR of 32.05. rs7929627 (IVS7-103A/G) and rs3825017 (N82N) showed an association with hyperuricaemia with ORs of 2.56 and 2.29, respectively. rs11602903 (788A/T) and rs121907892 (W258X) were negatively correlated with hyperuricaemia with ORs of 0.350 and 0.447, respectively. Individuals carrying the GATAG haplotype (n=32)—a relatively common variant consisting of rs7929627, rs75786299 and rs3825017—showed the highest risk for hyperuricaemia with an OR of 92.23 (p=9.55×10−3).ConclusionsThese results indicate that five newly described SNPs in the hURAT1 gene are significantly associated with uric acid level (4-2008-0318 and 4-2011-0277). |
| doi_str_mv | 10.1136/bmjopen-2015-009360 |
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This case–control study was designed to analyse whether hURAT1 might also be a candidate gene for hyperuricaemia or hypouricaemia.SettingWe recruited 68 healthy volunteers and divided them into two groups: a normal uric acid group and a hyperuricaemia group. We analysed the sequence of the URAT1 gene and found five significant single nucleotide polymorphisms (SNPs). We then selected 900 male subjects from the 262 200 enrolled in the Korean Cancer Prevention Study-II (KCPS-II) cohort for further genetic analysis.ParticipantsDNA samples from 36 individuals with normal uric acid (<4.5 mg/dL) and 32 individuals with hyperuricaemia (>8.5 mg/dL) were sequenced. Five significant SNPs (rs7929627, rs75786299, rs3825017, rs11602903 and rs121907892) were identified. We then chose 900 subjects from the KCPS-II cohort consisting of 450 subjects with normal uric acid (UA <4.1 mg/dL) and 450 subjects with hyperuricaemia (UA >8.7 mg/dL). The groups were matched by age, body mass index, metabolic syndrome and use of anti-hypertensive medication.Primary outcome measuresWe compared the OR of the incidence of hyperuricaemia by URAT1 genotype.ResultsThe strongest association with hyperuricaemia was observed for rs75786299 (IVS3+11A/G) with an OR of 32.05. rs7929627 (IVS7-103A/G) and rs3825017 (N82N) showed an association with hyperuricaemia with ORs of 2.56 and 2.29, respectively. rs11602903 (788A/T) and rs121907892 (W258X) were negatively correlated with hyperuricaemia with ORs of 0.350 and 0.447, respectively. Individuals carrying the GATAG haplotype (n=32)—a relatively common variant consisting of rs7929627, rs75786299 and rs3825017—showed the highest risk for hyperuricaemia with an OR of 92.23 (p=9.55×10−3).ConclusionsThese results indicate that five newly described SNPs in the hURAT1 gene are significantly associated with uric acid level (4-2008-0318 and 4-2011-0277).</description><identifier>ISSN: 2044-6055</identifier><identifier>EISSN: 2044-6055</identifier><identifier>DOI: 10.1136/bmjopen-2015-009360</identifier><identifier>PMID: 26603249</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Adult ; Alleles ; Asian Continental Ancestry Group - genetics ; Body mass index ; Case-Control Studies ; Cholesterol ; Disease prevention ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Hyperuricemia - blood ; Hyperuricemia - genetics ; Kidney stones ; Male ; Metabolism ; Mutation ; Odds Ratio ; Organic Anion Transporters - genetics ; Organic Cation Transport Proteins - genetics ; Pharmacology and Therapeutics ; Phenotype ; Polymorphism, Single Nucleotide ; Population ; Republic of Korea ; Rheumatism ; Studies ; Uric acid ; Uric Acid - blood ; White people ; Young Adult</subject><ispartof>BMJ open, 2015-11, Vol.5 (11), p.e009360-e009360</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ 2015 This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b538t-3cb5a8d78f5c2142f65ad8c78c5485aa6cad23d30f6a0ef3cdf7027ddedf7fb13</citedby><cites>FETCH-LOGICAL-b538t-3cb5a8d78f5c2142f65ad8c78c5485aa6cad23d30f6a0ef3cdf7027ddedf7fb13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://bmjopen.bmj.com/content/5/11/e009360.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttp://bmjopen.bmj.com/content/5/11/e009360.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27549,27550,27924,27925,53791,53793,77601,77632</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26603249$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Sung Kweon</creatorcontrib><creatorcontrib>Kim, Soriul</creatorcontrib><creatorcontrib>Chung, Jae-Yong</creatorcontrib><creatorcontrib>Jee, Sun Ha</creatorcontrib><title>Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1</title><title>BMJ open</title><addtitle>BMJ Open</addtitle><description>ObjectivesHuman urate transporter 1 (URAT1) is a member of the organic anion transporter family (SLC22A12) that primarily regulates the renal tubular reabsorption of uric acid. This case–control study was designed to analyse whether hURAT1 might also be a candidate gene for hyperuricaemia or hypouricaemia.SettingWe recruited 68 healthy volunteers and divided them into two groups: a normal uric acid group and a hyperuricaemia group. We analysed the sequence of the URAT1 gene and found five significant single nucleotide polymorphisms (SNPs). We then selected 900 male subjects from the 262 200 enrolled in the Korean Cancer Prevention Study-II (KCPS-II) cohort for further genetic analysis.ParticipantsDNA samples from 36 individuals with normal uric acid (<4.5 mg/dL) and 32 individuals with hyperuricaemia (>8.5 mg/dL) were sequenced. Five significant SNPs (rs7929627, rs75786299, rs3825017, rs11602903 and rs121907892) were identified. We then chose 900 subjects from the KCPS-II cohort consisting of 450 subjects with normal uric acid (UA <4.1 mg/dL) and 450 subjects with hyperuricaemia (UA >8.7 mg/dL). The groups were matched by age, body mass index, metabolic syndrome and use of anti-hypertensive medication.Primary outcome measuresWe compared the OR of the incidence of hyperuricaemia by URAT1 genotype.ResultsThe strongest association with hyperuricaemia was observed for rs75786299 (IVS3+11A/G) with an OR of 32.05. rs7929627 (IVS7-103A/G) and rs3825017 (N82N) showed an association with hyperuricaemia with ORs of 2.56 and 2.29, respectively. rs11602903 (788A/T) and rs121907892 (W258X) were negatively correlated with hyperuricaemia with ORs of 0.350 and 0.447, respectively. Individuals carrying the GATAG haplotype (n=32)—a relatively common variant consisting of rs7929627, rs75786299 and rs3825017—showed the highest risk for hyperuricaemia with an OR of 92.23 (p=9.55×10−3).ConclusionsThese results indicate that five newly described SNPs in the hURAT1 gene are significantly associated with uric acid level (4-2008-0318 and 4-2011-0277).</description><subject>Adult</subject><subject>Alleles</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Body mass index</subject><subject>Case-Control Studies</subject><subject>Cholesterol</subject><subject>Disease prevention</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Hyperuricemia - blood</subject><subject>Hyperuricemia - genetics</subject><subject>Kidney stones</subject><subject>Male</subject><subject>Metabolism</subject><subject>Mutation</subject><subject>Odds Ratio</subject><subject>Organic Anion Transporters - genetics</subject><subject>Organic Cation Transport Proteins - genetics</subject><subject>Pharmacology and Therapeutics</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Republic of Korea</subject><subject>Rheumatism</subject><subject>Studies</subject><subject>Uric acid</subject><subject>Uric Acid - blood</subject><subject>White people</subject><subject>Young Adult</subject><issn>2044-6055</issn><issn>2044-6055</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>ACMMV</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkVtLHTEUhYNUVKy_QJBAX_oyNvfJeSmI9gZSxctzyCQ77RxmJqfJzCn---Y4R9E-uV_2hnxrsXcWQseUnFLK1aemX8YVDBUjVFaELLgiO-iAESEqRaR892LeR0c5L0kpIRdSsj20z5QinInFAbq-aLOLa0gPOAZ8f3N2R_Htz-uM7eCxzTm61o5tHHAD41-AAWdIU4-n1DpsXetxB2voZvxR_R7tBttlONr2Q3T_9cvd-ffq8urbj_Ozy6qRXI8Vd4202tc6SMeoYEFJ67WrtZNCS2uVs55xz0lQlkDgzoeasNp7KENoKD9En2ff1dT04B0MY7KdWaW2t-nBRNua1y9D-9v8imsjlOJC6GLwcWuQ4p8J8mj68hXQdXaAOGVDa66UJjVVBf3wH7qMUxrKeYZqRTQjmmwM-Uy5FHNOEJ6XocRsQjPb0MwmNDOHVlQnL-941jxFVIDTGSjqNzn-AxkKowg</recordid><startdate>20151124</startdate><enddate>20151124</enddate><creator>Cho, Sung Kweon</creator><creator>Kim, Soriul</creator><creator>Chung, Jae-Yong</creator><creator>Jee, Sun Ha</creator><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</general><scope>9YT</scope><scope>ACMMV</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><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151124</creationdate><title>Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1</title><author>Cho, Sung Kweon ; Kim, Soriul ; Chung, Jae-Yong ; Jee, Sun Ha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b538t-3cb5a8d78f5c2142f65ad8c78c5485aa6cad23d30f6a0ef3cdf7027ddedf7fb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Body mass index</topic><topic>Case-Control Studies</topic><topic>Cholesterol</topic><topic>Disease prevention</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Hyperuricemia - blood</topic><topic>Hyperuricemia - genetics</topic><topic>Kidney stones</topic><topic>Male</topic><topic>Metabolism</topic><topic>Mutation</topic><topic>Odds Ratio</topic><topic>Organic Anion Transporters - genetics</topic><topic>Organic Cation Transport Proteins - genetics</topic><topic>Pharmacology and Therapeutics</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Republic of Korea</topic><topic>Rheumatism</topic><topic>Studies</topic><topic>Uric acid</topic><topic>Uric Acid - blood</topic><topic>White people</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cho, Sung Kweon</creatorcontrib><creatorcontrib>Kim, Soriul</creatorcontrib><creatorcontrib>Chung, Jae-Yong</creatorcontrib><creatorcontrib>Jee, Sun Ha</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BMJ open</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Sung Kweon</au><au>Kim, Soriul</au><au>Chung, Jae-Yong</au><au>Jee, Sun Ha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1</atitle><jtitle>BMJ open</jtitle><addtitle>BMJ Open</addtitle><date>2015-11-24</date><risdate>2015</risdate><volume>5</volume><issue>11</issue><spage>e009360</spage><epage>e009360</epage><pages>e009360-e009360</pages><issn>2044-6055</issn><eissn>2044-6055</eissn><abstract>ObjectivesHuman urate transporter 1 (URAT1) is a member of the organic anion transporter family (SLC22A12) that primarily regulates the renal tubular reabsorption of uric acid. This case–control study was designed to analyse whether hURAT1 might also be a candidate gene for hyperuricaemia or hypouricaemia.SettingWe recruited 68 healthy volunteers and divided them into two groups: a normal uric acid group and a hyperuricaemia group. We analysed the sequence of the URAT1 gene and found five significant single nucleotide polymorphisms (SNPs). We then selected 900 male subjects from the 262 200 enrolled in the Korean Cancer Prevention Study-II (KCPS-II) cohort for further genetic analysis.ParticipantsDNA samples from 36 individuals with normal uric acid (<4.5 mg/dL) and 32 individuals with hyperuricaemia (>8.5 mg/dL) were sequenced. Five significant SNPs (rs7929627, rs75786299, rs3825017, rs11602903 and rs121907892) were identified. We then chose 900 subjects from the KCPS-II cohort consisting of 450 subjects with normal uric acid (UA <4.1 mg/dL) and 450 subjects with hyperuricaemia (UA >8.7 mg/dL). The groups were matched by age, body mass index, metabolic syndrome and use of anti-hypertensive medication.Primary outcome measuresWe compared the OR of the incidence of hyperuricaemia by URAT1 genotype.ResultsThe strongest association with hyperuricaemia was observed for rs75786299 (IVS3+11A/G) with an OR of 32.05. rs7929627 (IVS7-103A/G) and rs3825017 (N82N) showed an association with hyperuricaemia with ORs of 2.56 and 2.29, respectively. rs11602903 (788A/T) and rs121907892 (W258X) were negatively correlated with hyperuricaemia with ORs of 0.350 and 0.447, respectively. Individuals carrying the GATAG haplotype (n=32)—a relatively common variant consisting of rs7929627, rs75786299 and rs3825017—showed the highest risk for hyperuricaemia with an OR of 92.23 (p=9.55×10−3).ConclusionsThese results indicate that five newly described SNPs in the hURAT1 gene are significantly associated with uric acid level (4-2008-0318 and 4-2011-0277).</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>26603249</pmid><doi>10.1136/bmjopen-2015-009360</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Alleles Asian Continental Ancestry Group - genetics Body mass index Case-Control Studies Cholesterol Disease prevention Genetic Predisposition to Disease Genotype Haplotypes Humans Hyperuricemia - blood Hyperuricemia - genetics Kidney stones Male Metabolism Mutation Odds Ratio Organic Anion Transporters - genetics Organic Cation Transport Proteins - genetics Pharmacology and Therapeutics Phenotype Polymorphism, Single Nucleotide Population Republic of Korea Rheumatism Studies Uric acid Uric Acid - blood White people Young Adult |
| title | Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1 |
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