Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).
Association of genomic loci from a cardiovascular gene SNP array with fibrinogen levels in European Americans and African-Americans from six cohort studies: the Candidate Gene Association Resource (CARe).
复制标题
DOI：
10.1182/blood-2010-06-289546
复制
发表时间：
2011-01
期刊：
影响因子：
20.3
通讯作者：
C. Wassel;L. Lange;B. Keating;K. Taylor;Andrew D. Johnson;Cameron D. Palmer;Lindsey A. Ho;N. Smith;E. Lange;Yun Li;Qiong Yang;J. Delaney;Weihong Tang;G. Tofler;S. Redline;H. Taylor;James G. Wilson;R. Tracy;D. Jacobs;A. Folsom;D. Green;C. O’Donnell;A. Reiner
中科院分区：
文献类型：
--
作者：
C. Wassel;L. Lange;B. Keating;K. Taylor;Andrew D. Johnson;Cameron D. Palmer;Lindsey A. Ho;N. Smith;E. Lange;Yun Li;Qiong Yang;J. Delaney;Weihong Tang;G. Tofler;S. Redline;H. Taylor;James G. Wilson;R. Tracy;D. Jacobs;A. Folsom;D. Green;C. O’Donnell;A. Reiner
几个常见的基因组位点，涉及各种免疫和代谢相关基因，已与血浆纤维蛋白原在欧洲裔美国人（EAs）。非裔美国人（AAs）纤维蛋白原的遗传决定因素的特点很差。使用血管基因中心阵列在23，634 EA和6657 AA参与者从6个研究组成的候选基因关联资源项目，我们检查了47，539常见和较低频率的变异与纤维蛋白原浓度的关联。我们在FGB（rs6054）中发现了一种罕见的Pro265 Leu变异体，与较低的纤维蛋白原相关。常见的纤维蛋白原基因单核苷酸多态性（FGB rs 1800787和FGG rs 2066861）显着相关的纤维蛋白原在EA中普遍存在于AA中，并显示出一致的关联。与较低纤维蛋白原相关的几个纤维蛋白原基因座单核苷酸多态性是AA独有的;其中包括新报告的与FGA rs 10050257的相关性。对于IL 6 R、IL 1 RN和NLRP 3炎性基因位点，EA和AA与纤维蛋白原的相关性一致，但在其他位点（CPS 1、PCCB和SCL 22 A5-IRF 1）则不一致。FGG rs 2066861与纤维蛋白原的相关性根据用于测量纤维蛋白原的测定类型而不同。进一步表征导致纤维蛋白原表型人群间差异的常见和较低频率的遗传变异可能有助于完善我们对止血和炎症对动脉粥样硬化血栓形成风险的贡献的理解。
Several common genomic loci, involving various immunity- and metabolism-related genes, have been associated with plasma fibrinogen in European Americans (EAs). The genetic determinants of fibrinogen in African Americans (AAs) are poorly characterized. Using a vascular gene-centric array in 23,634 EA and 6657 AA participants from 6 studies comprising the Candidate Gene Association Resource project, we examined the association of 47,539 common and lower frequency variants with fibrinogen concentration. We identified a rare Pro265Leu variant in FGB (rs6054) associated with lower fibrinogen. Common fibrinogen gene single nucleotide polymorphisms (FGB rs1800787 and FGG rs2066861) significantly associated with fibrinogen in EAs were prevalent in AAs and showed consistent associations. Several fibrinogen locus single nucleotide polymorphism associated with lower fibrinogen were exclusive to AAs; these include a newly reported association with FGA rs10050257. For IL6R, IL1RN, and NLRP3 inflammatory gene loci, associations with fibrinogen were concordant between EAs and AAs, but not at other loci (CPS1, PCCB, and SCL22A5-IRF1). The association of FGG rs2066861 with fibrinogen differed according to assay type used to measure fibrinogen. Further characterization of common and lower-frequency genetic variants that contribute to interpopulation differences in fibrinogen phenotype may help refine our understanding of the contribution of hemostasis and inflammation to atherothrombotic risk.