Assessment of genetic determinants of the association of γ' fibrinogen in relation to cardiovascular disease.

Abstract

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.

CONCLUSIONS:

γ' fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.

• Authors: Rehana S Lovely, Qiong Yang, Joseph M Massaro, Jing Wang, Ralph B D'Agostino Sr, Christopher J O'Donnell, Jackilen Shannon, David H Farrell
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 31 Issue 10 Pg. 2345-52 (Oct 2011) ISSN: 1524-4636 [Electronic] United States
• PMID: 21757653 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinogens, Abnormal
• fibrinogen gamma'

Topics

• Aged
• Cardiovascular Diseases (blood, epidemiology, genetics)
• Cohort Studies
• Female
• Fibrinogens, Abnormal (analysis, genetics)
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Logistic Models
• Male
• Massachusetts (epidemiology)
• Middle Aged
• Odds Ratio
• Phenotype
• Polymorphism, Single Nucleotide
• Prevalence
• Risk Assessment
• Risk Factors