Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease.
Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease.
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DOI：
10.1371/journal.pone.0007729
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发表时间：
2009-11-05
期刊：
影响因子：
3.7
通讯作者：
Hengstenberg C
中科院分区：
文献类型：
--
作者：
Stark K;Reinhard W;Grassl M;Erdmann J;Schunkert H;Illig T;Hengstenberg C
最近，一项包括超过28，000名参与者的大型荟萃分析确定了与血清尿酸（UA）水平相关的9个不同位点。由于血清尿酸水平升高可能导致痛风，是冠状动脉疾病（CAD）和心肌梗死（MI）的一个可能的危险因素，我们进行了两个大的病例对照相关性分析与德国MI家庭研究的参与者。在第一项研究中，我们评估了痛风的定性特征与10个单核苷酸多态性（SNP）标记物的关联，这些标记物与UA血清水平相关。在第二项研究中，分析了相同的遗传多态性与CAD的相关性。来自德国MI家族研究的683名痛风患者和1,563名健康对照者进行了基因分型。从最近进行的血清UA水平的全基因组荟萃分析中确定了9个SNP（rs 12129861，rs780094，rs734553，rs 2231142，rs742132，rs 1183201，rs 12356193，rs 17300741和rs 505802）。此外，包括标记rs6855911，其在先前的研究中与我们的队列中的痛风相关。位于SLC 2A 9的SNP rs734553和rs6855911，以及已知为ABCG 2错义多态性的SNP rs 2231142与痛风相关（分别为p= 5.6*10−7，p = 1.1*10−7和p =1.3*10−3）。 在基因PDZK 1、GCKR、LRRC 16 A、SLC 17 A1-SLC 17 A3、SLC 16 A9、SLC 22 A11和SLC 22 A12中的其他SNP未达到显著性水平。在我们的1,473例CAD病例和1,241例无CAD对照的研究样本中，10个标志物中没有一个与CAD风险相关。SLC 2A 9和ABCG 2基因中的SNP标记被发现与痛风表型强烈相关。然而，在我们的研究样本中，并非所有影响血清UA水平的SNP标记都与痛风的临床表现直接相关。此外，在德国MI家族研究中，这些SNP均未显示与CAD风险相关。
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. 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. 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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DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
4.5
作者：
Conen D;Wietlisbach V;Bovet P;Shamlaye C;Riesen W;Paccaud F;Burnier M
通讯作者：
Burnier M
影响因子：
64.8
作者：
Enomoto, A;Kimura, H;Endou, H
通讯作者：
Endou, H
影响因子：
120.7
作者：
Fang, J;Alderman, MH
通讯作者：
Alderman, MH
影响因子：
4.8
作者：
Anzai, Naohiko;Ichida, Kimiyoshi;Sakurai, Hiroyuki
通讯作者：
Sakurai, Hiroyuki