Cargando…

Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease

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 infarct...

Descripción completa

Detalles Bibliográficos
Autores principales: Stark, Klaus, Reinhard, Wibke, Grassl, Martina, Erdmann, Jeanette, Schunkert, Heribert, Illig, Thomas, Hengstenberg, Christian
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766838/
https://www.ncbi.nlm.nih.gov/pubmed/19890391
http://dx.doi.org/10.1371/journal.pone.0007729
_version_ 1782173248324108288
author Stark, Klaus
Reinhard, Wibke
Grassl, Martina
Erdmann, Jeanette
Schunkert, Heribert
Illig, Thomas
Hengstenberg, Christian
author_facet Stark, Klaus
Reinhard, Wibke
Grassl, Martina
Erdmann, Jeanette
Schunkert, Heribert
Illig, Thomas
Hengstenberg, Christian
author_sort Stark, Klaus
collection PubMed
description 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.
format Text
id pubmed-2766838
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-27668382009-11-05 Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease Stark, Klaus Reinhard, Wibke Grassl, Martina Erdmann, Jeanette Schunkert, Heribert Illig, Thomas Hengstenberg, Christian PLoS One Research Article 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. Public Library of Science 2009-11-05 /pmc/articles/PMC2766838/ /pubmed/19890391 http://dx.doi.org/10.1371/journal.pone.0007729 Text en Stark et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Stark, Klaus
Reinhard, Wibke
Grassl, Martina
Erdmann, Jeanette
Schunkert, Heribert
Illig, Thomas
Hengstenberg, Christian
Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
title Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
title_full Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
title_fullStr Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
title_full_unstemmed Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
title_short Common Polymorphisms Influencing Serum Uric Acid Levels Contribute to Susceptibility to Gout, but Not to Coronary Artery Disease
title_sort common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766838/
https://www.ncbi.nlm.nih.gov/pubmed/19890391
http://dx.doi.org/10.1371/journal.pone.0007729
work_keys_str_mv AT starkklaus commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease
AT reinhardwibke commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease
AT grasslmartina commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease
AT erdmannjeanette commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease
AT schunkertheribert commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease
AT illigthomas commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease
AT hengstenbergchristian commonpolymorphismsinfluencingserumuricacidlevelscontributetosusceptibilitytogoutbutnottocoronaryarterydisease