Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
| Autor: | Wibke Reinhard, Klaus Stark, Christian Hengstenberg, Jeanette Erdmann, Heribert Schunkert, Thomas Illig, Martina Grassl |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Gout Glucose Transport Proteins Facilitative Cardiovascular Disorders/Coronary Artery Disease lcsh:Medicine Genome-wide association study Coronary Artery Disease Gastroenterology chemistry.chemical_compound 0302 clinical medicine ATP Binding Cassette Transporter Subfamily G Member 2 030212 general & internal medicine lcsh:Science Genetics and Genomics/Genetics of Disease Aged 80 and over 0303 health sciences Multidisciplinary biology Middle Aged Neoplasm Proteins 3. Good health Female SLC22A12 Cardiovascular Disorders/Myocardial Infarction Research Article Adult medicine.medical_specialty Single-nucleotide polymorphism Genetics and Genomics/Complex Traits Polymorphism Single Nucleotide 03 medical and health sciences Internal medicine Genetics and Genomics/Population Genetics medicine Humans Genetic Predisposition to Disease Risk factor Aged 030304 developmental biology Polymorphism Genetic lcsh:R Case-control study medicine.disease Uric Acid Endocrinology chemistry Case-Control Studies biology.protein Uric acid ATP-Binding Cassette Transporters lcsh:Q Genome-Wide Association Study SLC2A9 |
| Zdroj: | PLoS ONE, Vol 4, Iss 11, p e7729 (2009) PLoS ONE 4:e7729 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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