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| PMID |
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| TITLE |
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| Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. |
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| ABSTRACT |
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| Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2009/03/05 |
| accepted |
2009/05/04 |
| epublish |
2009/06/05 |
| entrez |
2009/06/09 09:00 |
| pubmed |
2009/06/09 09:00 |
| medline |
2009/07/25 09:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Kolz M |
|
Kolz |
Melanie |
M |
|
Institute of Epidemiology, Helmholtz Zentrum München, National Research Center for Environment and Health, Neuherberg, Germany. |
| Johnson T |
|
Johnson |
Toby |
T |
|
|
| Sanna S |
|
Sanna |
Serena |
S |
|
|
| Teumer A |
|
Teumer |
Alexander |
A |
|
|
| Vitart V |
|
Vitart |
Veronique |
V |
|
|
| Perola M |
|
Perola |
Markus |
M |
|
|
| Mangino M |
|
Mangino |
Massimo |
M |
|
|
| Albrecht E |
|
Albrecht |
Eva |
E |
|
|
| Wallace C |
|
Wallace |
Chris |
C |
|
|
| Farrall M |
|
Farrall |
Martin |
M |
|
|
| Johansson A |
|
Johansson |
Asa |
A |
|
|
| Nyholt DR |
|
Nyholt |
Dale R |
DR |
|
|
| Aulchenko Y |
|
Aulchenko |
Yurii |
Y |
|
|
| Beckmann JS |
|
Beckmann |
Jacques S |
JS |
|
|
| Bergmann S |
|
Bergmann |
Sven |
S |
|
|
| Bochud M |
|
Bochud |
Murielle |
M |
|
|
| Brown M |
|
Brown |
Morris |
M |
|
|
| Campbell H |
|
Campbell |
Harry |
H |
|
|
|
EUROSPAN Consortium |
|
|
|
|
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| Connell J |
|
Connell |
John |
J |
|
|
| Dominiczak A |
|
Dominiczak |
Anna |
A |
|
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| Homuth G |
|
Homuth |
Georg |
G |
|
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| Lamina C |
|
Lamina |
Claudia |
C |
|
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| McCarthy MI |
|
McCarthy |
Mark I |
MI |
|
|
|
ENGAGE Consortium |
|
|
|
|
|
| Meitinger T |
|
Meitinger |
Thomas |
T |
|
|
| Mooser V |
|
Mooser |
Vincent |
V |
|
|
| Munroe P |
|
Munroe |
Patricia |
P |
|
|
| Nauck M |
|
Nauck |
Matthias |
M |
|
|
| Peden J |
|
Peden |
John |
J |
|
|
| Prokisch H |
|
Prokisch |
Holger |
H |
|
|
| Salo P |
|
Salo |
Perttu |
P |
|
|
| Salomaa V |
|
Salomaa |
Veikko |
V |
|
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| Samani NJ |
|
Samani |
Nilesh J |
NJ |
|
|
| Schlessinger D |
|
Schlessinger |
David |
D |
|
|
| Uda M |
|
Uda |
Manuela |
M |
|
|
| Völker U |
|
Völker |
Uwe |
U |
|
|
| Waeber G |
|
Waeber |
Gérard |
G |
|
|
| Waterworth D |
|
Waterworth |
Dawn |
D |
|
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| Wang-Sattler R |
|
Wang-Sattler |
Rui |
R |
|
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| Wright AF |
|
Wright |
Alan F |
AF |
|
|
| Adamski J |
|
Adamski |
Jerzy |
J |
|
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| Whitfield JB |
|
Whitfield |
John B |
JB |
|
|
| Gyllensten U |
|
Gyllensten |
Ulf |
U |
|
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| Wilson JF |
|
Wilson |
James F |
JF |
|
|
| Rudan I |
|
Rudan |
Igor |
I |
|
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| Pramstaller P |
|
Pramstaller |
Peter |
P |
|
|
| Watkins H |
|
Watkins |
Hugh |
H |
|
|
|
PROCARDIS Consortium |
|
|
|
|
|
| Doering A |
|
Doering |
Angela |
A |
|
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| Wichmann HE |
|
Wichmann |
H-Erich |
HE |
|
|
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KORA Study |
|
|
|
|
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| Spector TD |
|
Spector |
Tim D |
TD |
|
|
| Peltonen L |
|
Peltonen |
Leena |
L |
|
|
| Völzke H |
|
Völzke |
Henry |
H |
|
|
| Nagaraja R |
|
Nagaraja |
Ramaiah |
R |
|
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| Vollenweider P |
|
Vollenweider |
Peter |
P |
|
|
| Caulfield M |
|
Caulfield |
Mark |
M |
|
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|
WTCCC |
|
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|
|
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| Illig T |
|
Illig |
Thomas |
T |
|
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| Gieger C |
|
Gieger |
Christian |
C |
|
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| INVESTIGATORS |
|
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| JOURNAL |
|
| VOLUME: 5 |
| ISSUE: 6 |
| TITLE: PLoS genetics |
| ISOABBREVIATION: PLoS Genet. |
| YEAR: 2009 |
| MONTH: Jun |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1553-7404 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
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| MEDLINETA: PLoS Genet |
| COUNTRY: United States |
| ISSNLINKING: 1553-7390 |
| NLMUNIQUEID: 101239074 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Meta-Analysis |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
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| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| Cites |
Clin Chim Acta. 2000 Aug;298(1-2):55-68 |
10876004 |
|
| Cites |
Nutrition. 2009 Jan;25(1):51-7 |
18834718 |
|
| Cites |
Atherosclerosis. 2001 Apr;155(2):283-90 |
11254897 |
|
| Cites |
Nature. 2002 May 23;417(6887):447-52 |
12024214 |
|
| Cites |
Pflugers Arch. 2004 Feb;447(5):619-28 |
12739169 |
|
| Cites |
J Pharmacol Sci. 2004 Mar;94(3):297-304 |
15037815 |
|
| Cites |
Life Sci. 2004 Jul 23;75(10):1243-53 |
15219812 |
|
| Cites |
J Biol Chem. 2004 Oct 29;279(44):45942-50 |
15304510 |
|
| Cites |
Acta Genet Med Gemellol (Roma). 1983;32(2):117-26 |
6685961 |
|
| Cites |
Arch Gerontol Geriatr. 1984 Dec;3(4):321-48 |
6532339 |
|
| Cites |
Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10045-8 |
1658794 |
|
| Cites |
JAMA. 1991 Dec 4;266(21):3008-11 |
1820474 |
|
| Cites |
Br J Pharmacol. 1992 Dec;107(4):1192-7 |
1334752 |
|
| Cites |
Clin Sci (Lond). 1997 Jan;92(1):51-8 |
9038591 |
|
| Cites |
Eur J Pharmacol. 1998 Jan 26;342(2-3):235-9 |
9548391 |
|
| Cites |
Biochem Pharmacol. 1999 Oct 15;58(8):1361-70 |
10487540 |
|
| Cites |
Biochem J. 1999 Oct 15;343 Pt 2:281-99 |
10510291 |
|
| Cites |
Curr Rheumatol Rep. 2005 Jun;7(3):227-34 |
15919000 |
|
| Cites |
Dev Cell. 2005 Aug;9(2):209-21 |
16054028 |
|
| Cites |
Ann Intern Med. 2005 Oct 4;143(7):499-516 |
16204163 |
|
| Cites |
Scand J Immunol. 2006 Dec;64(6):639-45 |
17083620 |
|
| Cites |
Curr Opin Rheumatol. 2007 Mar;19(2):151-7 |
17278930 |
|
| Cites |
Science. 2007 Jun 1;316(5829):1331-6 |
17463246 |
|
| Cites |
Nat Genet. 2007 Jul;39(7):906-13 |
17572673 |
|
| Cites |
Diabetologia. 2008 Jan;51(1):70-5 |
18008060 |
|
| Cites |
Am J Hum Genet. 2008 Jan;82(1):139-49 |
18179892 |
|
| Cites |
Clin Chem. 2008 Feb;54(2):231-3 |
18223129 |
|
| Cites |
Curr Opin Rheumatol. 2008 Mar;20(2):192-7 |
18349750 |
|
| Cites |
Nat Genet. 2008 Apr;40(4):430-6 |
18327256 |
|
| Cites |
Nat Genet. 2008 Apr;40(4):437-42 |
18327257 |
|
| Cites |
PLoS Genet. 2007 Nov;3(11):e194 |
17997608 |
|
| Cites |
Genet Epidemiol. 2008 Apr;32(3):227-34 |
18300295 |
|
| Cites |
Diabetes. 2008 Aug;57(8):2253-7 |
18556336 |
|
| Cites |
Diabetes. 2008 Nov;57(11):3112-21 |
18678614 |
|
| Cites |
PLoS Med. 2008 Oct 7;5(10):e197 |
18842065 |
|
| Cites |
FEBS Lett. 2008 Nov 12;582(27):3811-6 |
18948099 |
|
| Cites |
PLoS Genet. 2008 Nov;4(11):e1000282 |
19043545 |
|
| Cites |
Lancet. 2008 Dec 6;372(9654):1953-61 |
18834626 |
|
| Cites |
Am J Hum Genet. 2000 Jun;66(6):1933-44 |
10801388 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 076113/B/04/Z |
Wellcome Trust |
United Kingdom |
| AA007535 |
NIAAA NIH HHS |
United States |
| CZB/4/710 |
Chief Scientist Office |
United Kingdom |
| FS/05/061/19501 |
British Heart Foundation |
United Kingdom |
| G0400874 |
Medical Research Council |
United Kingdom |
| G9521010 |
Medical Research Council |
United Kingdom |
| G9521010D |
Medical Research Council |
United Kingdom |
| MC_U127561128 |
Medical Research Council |
United Kingdom |
| N01-AG-1-2109 |
NIA NIH HHS |
United States |
| PG02/128 |
British Heart Foundation |
United Kingdom |
|
Arthritis Research UK |
United Kingdom |
|
| GENERAL NOTE |
|
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| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Female |
|
| Genetic Variation |
|
| Genome-Wide Association Study |
|
| Gout |
etiology |
| Humans |
etiology |
| Male |
etiology |
| Uric Acid |
blood |
|
| SUPPLEMENTARY MESH |
|
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| GENE SYMBOLS |
|
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| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 268B43MJ25 |
Uric Acid |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC2683940 |
NLM |
|
|
