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Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease.
PLoS ONE 4:e7729 (2009)
BACKGROUND: Recently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA) levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD) and myocardial infarction (MI), we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP) markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD. METHODS AND FINDINGS: A total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802). Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p=5.6*10(-7), p=1.1*10(-7), and p=1.3*10(-3), respectively). Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls. CONCLUSION: SNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; HEART-DISEASE; RISK; MORTALITY; SLC2A9; GENE; LOCUS
Language
english
Publication Year
2009
HGF-reported in Year
0
ISSN (print) / ISBN
1932-6203
Journal
PLoS ONE
Quellenangaben
Volume: 4,
Issue: 11,
Article Number: e7729
Publisher
Public Library of Science (PLoS)
Publishing Place
Lawrence, Kan.
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
POF-Topic(s)
30503 - Chronic Diseases of the Lung and Allergies
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-503900-003
PubMed ID
19890391
WOS ID
000271459700015
Erfassungsdatum
2009-12-15