RGD Reference Report - Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study. - Rat Genome Database

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Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study.

Authors: Carty, CL  Cushman, M  Jones, D  Lange, LA  Hindorff, LA  Rice, K  Jenny, NS  Durda, JP  Walston, J  Carlson, CS  Nickerson, D  Tracy, RP  Reiner, AP 
Citation: Carty CL, etal., Thromb Haemost. 2008 Feb;99(2):388-95.
RGD ID: 5688760
Pubmed: PMID:18278190   (View Abstract at PubMed)
DOI: DOI:10.1160/TH07-08-0523   (Journal Full-text)

Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated with fibrinogen concentration, carotid artery intima-medial thickness (IMT) and risk of incident myocardial infarction (MI), ischemic stroke and CVD mortality in European- (EA) and African-descent (AA) adults (> or = 65 years) from the Cardiovascular Health Study. TagSNPs were genotyped in 3,969 EA and 719 AA free of MI or stroke at baseline. Race-specific models included multiple testing correction and adjustment for sex, age and site. Among EA, minor alleles of FGA3807, FGB1437 and FGG902 were associated with higher fibrinogen levels; whereas FGA251, FGA2224, FGA6534 and FGG10034 were associated with lower levels, p<0.004 for each. Strongest associations were seen for FGB1437; each additional copy of the minor allele was associated with 13 mg/dl (95%CI: 9-16) higher fibrinogen level. Similar trends in AA were not significant. Fibrinogen haplotypes were not significantly associated with internal or common carotid IMT. No associations with MI or CVD mortality were seen in EA, though FGB1038 and FGG902 were significantly associated with increased and decreased risk of stroke in men, respectively, as were related haplotypes. FGB1038 was also associated with CVD mortality in AA, HR = 1.9 (95%CI: 1.3-2.7). In conclusion, while fibrinogen genetic variation was strongly associated with fibrinogen levels, there was less evidence of association with the more complex outcomes of IMT and CVD events.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiovascular system disease disease_progressionIAGP 5688760 RGD 
cardiovascular system disease disease_progressionISOFGB (Homo sapiens)5688760; 5688760 RGD 
Stroke susceptibilityIAGP 5688760DNA:SNP:promoter:1038G>A (rs1800791) (human)RGD 
Stroke susceptibilityIAGP 5688760DNA:SNP:promoter:902A>G (rs1800792) (human)RGD 
Stroke susceptibilityISOFGB (Homo sapiens)5688760; 5688760DNA:SNP:promoter:1038G>A (rs1800791) (human)RGD 
Stroke susceptibilityISOFGG (Homo sapiens)5688760; 5688760DNA:SNP:promoter:902A>G (rs1800792) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Ischemic stroke susceptibilityIAGP 5688760DNA:SNP:promoter:1038G>A (rs1800791)RGD 
Ischemic stroke susceptibilityIAGP 5688760DNA:SNP:promoter:902A>G (rs1800792)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Fgb  (fibrinogen beta chain)
Fgg  (fibrinogen gamma chain)

Genes (Mus musculus)
Fgb  (fibrinogen beta chain)
Fgg  (fibrinogen gamma chain)

Genes (Homo sapiens)
FGB  (fibrinogen beta chain)
FGG  (fibrinogen gamma chain)


Additional Information