新型基因位点与循环纤维蛋白原水平的关联：一项基于6个群体队列的全基因组关联研究
Association of novel genetic Loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts.
作者信息
Dehghan Abbas, Yang Qiong, Peters Annette, Basu Saonli, Bis Joshua C, Rudnicka Alicja R, Kavousi Maryam, Chen Ming-Huei, Baumert Jens, Lowe Gordon D O, McKnight Barbara, Tang Weihong, de Maat Moniek, Larson Martin G, Eyhermendy Susana, McArdle Wendy L, Lumley Thomas, Pankow James S, Hofman Albert, Massaro Joseph M, Rivadeneira Fernando, Kolz Melanie, Taylor Kent D, van Duijn Cornelia M, Kathiresan Sekar, Illig Thomas, Aulchenko Yurii S, Volcik Kelly A, Johnson Andrew D, Uitterlinden Andre G, Tofler Geoffrey H, Gieger Christian, Psaty Bruce M, Couper David J, Boerwinkle Eric, Koenig Wolfgang, O'Donnell Christopher J, Witteman Jacqueline C, Strachan David P, Smith Nicholas L, Folsom Aaron R
机构信息
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
出版信息
Circ Cardiovasc Genet. 2009 Apr;2(2):125-33. doi: 10.1161/CIRCGENETICS.108.825224.
BACKGROUND
Fibrinogen is both central to blood coagulation and an acute-phase reactant. We aimed to identify common variants influencing circulation fibrinogen levels.
METHODS AND RESULTS
We conducted a genome-wide association analysis on 6 population-based studies, the Rotterdam Study, the Framingham Heart Study, the Cardiovascular Health Study, the Atherosclerosis Risk in Communities Study, the Monitoring of Trends and Determinants in Cardiovascular Disease/KORA Augsburg Study, and the British 1958 Birth Cohort Study, including 22 096 participants of European ancestry. Four loci were marked by 1 or more single-nucleotide polymorphisms that demonstrated genome-wide significance (P<5.0 x 10(-8)). These included a single-nucleotide polymorphism located in the fibrinogen beta chain (FGB) gene and 3 single-nucleotide polymorphisms representing newly identified loci. The high-signal single-nucleotide polymorphisms were rs1800789 in exon 7 of FGB (P=1.8 x 10(-30)), rs2522056 downstream from the interferon regulatory factor 1 (IRF1) gene (P=1.3 x 10(-15)), rs511154 within intron 1 of the propionyl coenzyme A carboxylase (PCCB) gene (P=5.9 x 10(-10)), and rs1539019 on the NLR family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04 x 10(-8)).
CONCLUSIONS
Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease.
背景
纤维蛋白原在血液凝固中起核心作用，也是一种急性期反应物。我们旨在识别影响循环纤维蛋白原水平的常见变异。
方法与结果
我们对6项基于人群的研究进行了全基因组关联分析，这些研究包括鹿特丹研究、弗雷明汉心脏研究、心血管健康研究、社区动脉粥样硬化风险研究、心血管疾病趋势和决定因素监测/德国奥格斯堡KORA研究以及英国1958年出生队列研究，共纳入22096名欧洲血统参与者。有4个位点由1个或多个单核苷酸多态性标记，这些单核苷酸多态性具有全基因组显著性（P<5.0×10⁻⁸）。其中包括位于纤维蛋白原β链（FGB）基因中的一个单核苷酸多态性以及代表新发现位点的3个单核苷酸多态性。高信号单核苷酸多态性分别为FGB基因第7外显子中的rs1800789（P=1.8×10⁻³⁰）、干扰素调节因子1（IRF1）基因下游的rs2522056（P=1.3×10⁻¹⁵）、丙酰辅酶A羧化酶（PCCB）基因第1内含子中的rs511154（P=5.9×10⁻¹⁰）以及含3种亚型的NLR家族pyrin结构域（NLRP3）基因上的rs1539019（P=1.04×10⁻⁸）。
结论
我们的研究结果突出了在调节心血管疾病潜在炎症中可能重要的生物学途径。
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