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Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke.
J Thromb Haemost. 2009 Mar; 7(3):385-90.JT

Abstract

BACKGROUND

Confounding by common causes and reverse causation have been proposed as explanations for the association between high fibrinogen levels and cardiovascular disease. Genetic variants can alter fibrinogen characteristics and are not subject to these problems.

OBJECTIVES

To determine the fibrinogen plasma levels for genotypic variants in fibrinogen-A alpha (FGA Thr312Ala) and fibrinogen-B beta (FGB - 455G/A), and whether these variants are associated with arterial thrombosis.

METHODS

Fibrinogen genotypes were determined in a population-based case-control study including women aged 18-50 years; 218 cases with myocardial infarction, 192 cases with ischemic stroke, and 769 healthy controls. Fibrinogen levels were determined in the control population.

RESULTS

The FGB - 455G/A variant increased plasma fibrinogen levels, whereas the FGA Thr312Ala variant lowered plasma fibrinogen levels, albeit to a modest extent. The risk of ischemic stroke was altered when the homozygote minor allele was compared with the homozygote major allele. The FGA Thr312Ala single-nucleotide polymorphism (SNP) was associated with a decrease in risk [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.21-0.87], whereas the FGB - 455G/A SNP might have increased the risk (OR 1.76; 95% CI 0.7-4.03). The risk of myocardial infarction was not altered for either SNP (FGA Thr312Ala, OR 0.98, 95% CI 0.40-2.40; FGB - 455G/A, OR 0.98, 95% CI 0.40-2.40).

CONCLUSIONS

With the genetic variations as markers of plasma fibrinogen levels alterations, thereby ruling out confounding and reverse causation, our results suggest that plasma fibrinogen levels could play a more pronounced role as risk factors for ischemic stroke than for myocardial infarction.

Authors+Show Affiliations

Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19143925

Citation

Siegerink, B, et al. "Genetic Variation in Fibrinogen; Its Relationship to Fibrinogen Levels and the Risk of Myocardial Infarction and Ischemic Stroke." Journal of Thrombosis and Haemostasis : JTH, vol. 7, no. 3, 2009, pp. 385-90.
Siegerink B, Rosendaal FR, Algra A. Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke. J Thromb Haemost. 2009;7(3):385-90.
Siegerink, B., Rosendaal, F. R., & Algra, A. (2009). Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke. Journal of Thrombosis and Haemostasis : JTH, 7(3), 385-90. https://doi.org/10.1111/j.1538-7836.2008.03266.x
Siegerink B, Rosendaal FR, Algra A. Genetic Variation in Fibrinogen; Its Relationship to Fibrinogen Levels and the Risk of Myocardial Infarction and Ischemic Stroke. J Thromb Haemost. 2009;7(3):385-90. PubMed PMID: 19143925.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variation in fibrinogen; its relationship to fibrinogen levels and the risk of myocardial infarction and ischemic stroke. AU - Siegerink,B, AU - Rosendaal,F R, AU - Algra,A, PY - 2009/1/16/entrez PY - 2009/1/16/pubmed PY - 2009/4/30/medline SP - 385 EP - 90 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 7 IS - 3 N2 - BACKGROUND: Confounding by common causes and reverse causation have been proposed as explanations for the association between high fibrinogen levels and cardiovascular disease. Genetic variants can alter fibrinogen characteristics and are not subject to these problems. OBJECTIVES: To determine the fibrinogen plasma levels for genotypic variants in fibrinogen-A alpha (FGA Thr312Ala) and fibrinogen-B beta (FGB - 455G/A), and whether these variants are associated with arterial thrombosis. METHODS: Fibrinogen genotypes were determined in a population-based case-control study including women aged 18-50 years; 218 cases with myocardial infarction, 192 cases with ischemic stroke, and 769 healthy controls. Fibrinogen levels were determined in the control population. RESULTS: The FGB - 455G/A variant increased plasma fibrinogen levels, whereas the FGA Thr312Ala variant lowered plasma fibrinogen levels, albeit to a modest extent. The risk of ischemic stroke was altered when the homozygote minor allele was compared with the homozygote major allele. The FGA Thr312Ala single-nucleotide polymorphism (SNP) was associated with a decrease in risk [odds ratio (OR) 0.43; 95% confidence interval (CI) 0.21-0.87], whereas the FGB - 455G/A SNP might have increased the risk (OR 1.76; 95% CI 0.7-4.03). The risk of myocardial infarction was not altered for either SNP (FGA Thr312Ala, OR 0.98, 95% CI 0.40-2.40; FGB - 455G/A, OR 0.98, 95% CI 0.40-2.40). CONCLUSIONS: With the genetic variations as markers of plasma fibrinogen levels alterations, thereby ruling out confounding and reverse causation, our results suggest that plasma fibrinogen levels could play a more pronounced role as risk factors for ischemic stroke than for myocardial infarction. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/19143925/Genetic_variation_in_fibrinogen L2 - https://doi.org/10.1111/j.1538-7836.2008.03266.x DB - PRIME DP - Unbound Medicine ER -