TY - JOUR
T1 - Assessment of genetic determinants of the association of γ′ fibrinogen in relation to cardiovascular disease
AU - Lovely, Rehana S.
AU - Yang, Qiong
AU - Massaro, Joseph M.
AU - Wang, Jing
AU - D'Agostino, Ralph B.
AU - O'Donnell, Christopher J.
AU - Shannon, Jackilen
AU - Farrell, David H.
PY - 2011/10
Y1 - 2011/10
N2 - OBJECTIVE-: γ′ fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of γ′ fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort. METHODS AND RESULTS-: A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for γ′ fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0×10-8) for association with γ′ fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97×10-110) in the fibrinogen gene locus near FGG, which encodes the γ chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, γ′ fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. γ′ fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with γ′ fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB, which encodes the Bβ chain. CONCLUSION-: γ′ fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.
AB - OBJECTIVE-: γ′ fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of γ′ fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort. METHODS AND RESULTS-: A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for γ′ fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0×10-8) for association with γ′ fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97×10-110) in the fibrinogen gene locus near FGG, which encodes the γ chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, γ′ fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. γ′ fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with γ′ fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB, which encodes the Bβ chain. CONCLUSION-: γ′ fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.
KW - coronary heart disease
KW - epidemiology
KW - fibrin
KW - gene mutations
KW - risk factors
UR - http://www.scopus.com/inward/record.url?scp=80052963043&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.111.232710
DO - 10.1161/ATVBAHA.111.232710
M3 - Article
C2 - 21757653
AN - SCOPUS:80052963043
SN - 1079-5642
VL - 31
SP - 2345
EP - 2352
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 10
ER -