The GLUT9 Gene Is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts

High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quanti...

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Published in:	PLoS genetics Vol. 3; no. 11; p. e194
Main Authors:	Li, Siguang, Sanna, Serena, Maschio, Andrea, Busonero, Fabio, Usala, Gianluca, Mulas, Antonella, Lai, Sandra, Dei, Mariano, Orrù, Marco, Albai, Giuseppe, Bandinelli, Stefania, Schlessinger, David, Lakatta, Edward, Scuteri, Angelo, Najjar, Samer S, Guralnik, Jack, Naitza, Silvia, Crisponi, Laura, Cao, Antonio, Abecasis, Gonçalo, Ferrucci, Luigi, Uda, Manuela, Chen, Wei-Min, Nagaraja, Ramaiah
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01.11.2007 Public Library of Science (PLoS)
Subjects:	Adolescent Adult Aged Aged, 80 and over Cohort Studies Colleges & universities Deoxyribonucleic acid Diet DNA Female Genes Genetic testing Genetics and Genomics Genome, Human - genetics Genomes Genotype Glucose Glucose Transport Proteins, Facilitative - genetics Homo (Human) Humans Italy Linkage Disequilibrium Male Middle Aged Molecular Sequence Data Mortality Polymorphism, Single Nucleotide - genetics Population Proteins Uric Acid - blood Italy
ISSN:	1553-7404, 1553-7390, 1553-7404
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Abstract	High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 x 10(-16)), along with eight others (p = 7.75 x 10(-16) to 6.05 x 10(-11)). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.
AbstractList	High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 x [10.sup.-16]), along with eight others (p = 7.75 x [10.sup.-16] to 6.05 x [10.sup.-11]). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 x 10(-16)), along with eight others (p = 7.75 x 10(-16) to 6.05 x 10(-11)). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 x 10(-16)), along with eight others (p = 7.75 x 10(-16) to 6.05 x 10(-11)). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. High serum uric acid levels elevate pro-inflammatory–state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10−16), along with eight others (p = 7.75 × 10−16 to 6.05 × 10−11). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10-16), along with eight others (p = 7.75 × 10-16 to 6.05 × 10-11). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 x 10(-16)), along with eight others (p = 7.75 x 10(-16) to 6.05 x 10(-11)). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10-16), along with eight others (p = 7.75 × 10-16 to 6.05 × 10-11). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 x [10.sup.-16]), along with eight others (p = 7.75 x [10.sup.-16] to 6.05 x [10.sup.-11]). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. doi:10.1371/journal.pgen.0030194
Audience	Academic
Author	Cao, Antonio Uda, Manuela Scuteri, Angelo Chen, Wei-Min Bandinelli, Stefania Li, Siguang Abecasis, Gonçalo Crisponi, Laura Nagaraja, Ramaiah Lai, Sandra Guralnik, Jack Dei, Mariano Schlessinger, David Lakatta, Edward Naitza, Silvia Sanna, Serena Orrù, Marco Usala, Gianluca Albai, Giuseppe Najjar, Samer S Busonero, Fabio Maschio, Andrea Mulas, Antonella Ferrucci, Luigi
AuthorAffiliation	2 Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy 7 Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America 5 Unità Operativa Geriatria, Istituto Nazionale Ricovero e Cura Anziani, Rome, Italy 1 Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, United States of America 6 Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America 3 Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Florence, Italy 4 Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, United States of America 8 Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America University of Alabama at Birmingham, United States of America
AuthorAffiliation_xml	– name: 3 Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Florence, Italy – name: 8 Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America – name: 6 Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America – name: University of Alabama at Birmingham, United States of America – name: 4 Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, United States of America – name: 1 Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, United States of America – name: 5 Unità Operativa Geriatria, Istituto Nazionale Ricovero e Cura Anziani, Rome, Italy – name: 7 Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America – name: 2 Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy
Author_xml	– sequence: 1 givenname: Siguang surname: Li fullname: Li, Siguang – sequence: 2 givenname: Serena surname: Sanna fullname: Sanna, Serena – sequence: 3 givenname: Andrea surname: Maschio fullname: Maschio, Andrea – sequence: 4 givenname: Fabio surname: Busonero fullname: Busonero, Fabio – sequence: 5 givenname: Gianluca surname: Usala fullname: Usala, Gianluca – sequence: 6 givenname: Antonella surname: Mulas fullname: Mulas, Antonella – sequence: 7 givenname: Sandra surname: Lai fullname: Lai, Sandra – sequence: 8 givenname: Mariano surname: Dei fullname: Dei, Mariano – sequence: 9 givenname: Marco surname: Orrù fullname: Orrù, Marco – sequence: 10 givenname: Giuseppe surname: Albai fullname: Albai, Giuseppe – sequence: 11 givenname: Stefania surname: Bandinelli fullname: Bandinelli, Stefania – sequence: 12 givenname: David surname: Schlessinger fullname: Schlessinger, David – sequence: 13 givenname: Edward surname: Lakatta fullname: Lakatta, Edward – sequence: 14 givenname: Angelo surname: Scuteri fullname: Scuteri, Angelo – sequence: 15 givenname: Samer S surname: Najjar fullname: Najjar, Samer S – sequence: 16 givenname: Jack surname: Guralnik fullname: Guralnik, Jack – sequence: 17 givenname: Silvia surname: Naitza fullname: Naitza, Silvia – sequence: 18 givenname: Laura surname: Crisponi fullname: Crisponi, Laura – sequence: 19 givenname: Antonio surname: Cao fullname: Cao, Antonio – sequence: 20 givenname: Gonçalo surname: Abecasis fullname: Abecasis, Gonçalo – sequence: 21 givenname: Luigi surname: Ferrucci fullname: Ferrucci, Luigi – sequence: 22 givenname: Manuela surname: Uda fullname: Uda, Manuela – sequence: 23 givenname: Wei-Min surname: Chen fullname: Chen, Wei-Min – sequence: 24 givenname: Ramaiah surname: Nagaraja fullname: Nagaraja, Ramaiah
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/17997608$$D View this record in MEDLINE/PubMed
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Copyright	COPYRIGHT 2007 Public Library of Science 2007 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Li S, Sanna S, Maschio A, Busonero F, Usala G, et al. (2007) The GLUT9 Gene Is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts. PLoS Genet 3(11): e194. doi:10.1371/journal.pgen.0030194 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. 2007 2007 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Li S, Sanna S, Maschio A, Busonero F, Usala G, et al. (2007) The GLUT9 Gene Is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts. PLoS Genet 3(11): e194. doi:10.1371/journal.pgen.0030194
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Snippet	High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and... High serum uric acid levels elevate pro-inflammatory–state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and... High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and...
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SubjectTerms	Adolescent Adult Aged Aged, 80 and over Cohort Studies Colleges & universities Deoxyribonucleic acid Diet DNA Female Genes Genetic testing Genetics and Genomics Genome, Human - genetics Genomes Genotype Glucose Glucose Transport Proteins, Facilitative - genetics Homo (Human) Humans Italy Linkage Disequilibrium Male Middle Aged Molecular Sequence Data Mortality Polymorphism, Single Nucleotide - genetics Population Proteins Uric Acid - blood
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Title	The GLUT9 Gene Is Associated with Serum Uric Acid Levels in Sardinia and Chianti Cohorts
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