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Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors.

Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
TitleMultiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors.
Publication TypeJournal Article
Year of Publication2010
AuthorsYang, Q, Köttgen, A, Dehghan, A, Smith, AV, Glazer, NL, Chen, M-H, Chasman, DI, Aspelund, T, Eiriksdottir, G, Harris, TB, Launer, L, Nalls, M, Hernandez, D, Arking, DE, Boerwinkle, E, Grove, ML, Li, M, Kao, WHLinda, Chonchol, M, Haritunians, T, Li, G, Lumley, T, Psaty, BM, Shlipak, M, Hwang, S-J, Larson, MG, O'Donnell, CJ, Upadhyay, A, van Duijn, CM, Hofman, A, Rivadeneira, F, Stricker, B, Uitterlinden, AG, Paré, G, Parker, AN, Ridker, PM, Siscovick, DS, Gudnason, V, Witteman, JC, Fox, CS, Coresh, J
JournalCirc Cardiovasc Genet
Volume3
Issue6
Pagination523-30
Date Published2010 Dec
ISSN1942-3268
KeywordsCardiovascular Diseases, Coronary Disease, Female, Genetic Loci, Genome-Wide Association Study, Gout, Humans, Male, Risk Factors, Uric Acid
Abstract<p><b>BACKGROUND: </b>Elevated serum urate levels can lead to gout and are associated with cardiovascular risk factors. We performed a genome-wide association study to search for genetic susceptibility loci for serum urate and gout and investigated the causal nature of the associations of serum urate with gout and selected cardiovascular risk factors and coronary heart disease (CHD).</p><p><b>METHODS AND RESULTS: </b>Meta-analyses of genome-wide association studies (GWAS) were performed in 5 population-based cohorts of the Cohorts for Heart and Aging Research in Genome Epidemiology consortium for serum urate and gout in 28 283 white participants. The effect of the most significant single-nucleotide polymorphism at all genome-wide significant loci on serum urate was added to create a genetic urate score. Findings were replicated in the Women's Genome Health Study (n=22 054). Single-nucleotide polymorphisms at 8 genetic loci achieved genome-wide significance with serum urate levels (P=4×10(-8) to 2×10(-242) in SLC22A11, GCKR, R3HDM2-INHBC region, RREB1, PDZK1, SLC2A9, ABCG2, and SLC17A1). Only 2 loci (SLC2A9, ABCG2) showed genome-wide significant association with gout. The genetic urate score was strongly associated with serum urate and gout (odds ratio, 12.4 per 100 μmol/L; P=3×10(-39)) but not with blood pressure, glucose, estimated glomerular filtration rate, chronic kidney disease, or CHD. The lack of association between the genetic score and the latter phenotypes also was observed in the Women's Genome Health Study.</p><p><b>CONCLUSIONS: </b>The genetic urate score analysis suggested a causal relationship between serum urate and gout but did not provide evidence for one between serum urate and cardiovascular risk factors and CHD.</p>
DOI10.1161/CIRCGENETICS.109.934455
Alternate JournalCirc Cardiovasc Genet
PubMed ID20884846
PubMed Central IDPMC3371395
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
K01 DK067207 / DK / NIDDK NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
N01 AG012100 / AG / NIA NIH HHS / United States
N01 HC-25195 / HC / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HL 043851 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL043851 / HL / NHLBI NIH HHS / United States
UL1 RR 025005 / RR / NCRR NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
M01 RR000069 / RR / NCRR NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
R01 HL091069 / HL / NHLBI NIH HHS / United States
N02 HL64278 / HL / NHLBI NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 EY017362 / EY / NEI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
CA 047988 / CA / NCI NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
K01DK067207 / DK / NIDDK NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01DK076770 / DK / NIDDK NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01 NS061836 / NS / NINDS NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
M01RR00069 / RR / NCRR NIH HHS / United States
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
R01 HL080467 / HL / NHLBI NIH HHS / United States
U01 HL069757 / HL / NHLBI NIH HHS / United States
R01 DK076770 / DK / NIDDK NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
R01 AG027002 / AG / NIA NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N02-HL-64278 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States

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