Association of Novel Genetic Loci With Circulating Fibrinogen LevelsCLINICAL PERSPECTIVE

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 <5.0×10−8). These included a single-nucleotide polymorphism located in the fibrinogen β 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 =1.8×10−30), rs2522056 downstream from the interferon regulatory factor 1 ( IRF1 ) gene ( P =1.3×10−15), rs511154 within intron 1 of the propionyl coenzyme A carboxylase ( PCCB ) gene ( P =5.9×10−10), and rs1539019 on the NLR family pyrin domain containing 3 isoforms ( NLRP3 ) gene ( P =1.04×10−8). Conclusions— Our findings highlight biological pathways that may be important in regulation of inflammation underlying cardiovascular disease. Received October 1, 2008; accepted January 5, 2009. # CLINICAL PERSPECTIVE {#article-title-2}