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Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts.
Stroke. 2005 Aug; 36(8):1661-5.S

Abstract

BACKGROUND AND PURPOSE

Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke.

METHODS

A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene.

RESULTS

The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke.

CONCLUSIONS

Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.

Authors+Show Affiliations

Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden. pg.wiklund@medicin.umu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16020771

Citation

Wiklund, Per-Gunnar, et al. "Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke: Replicated Findings in Two Nested Case-control Studies Based On Independent Cohorts." Stroke, vol. 36, no. 8, 2005, pp. 1661-5.
Wiklund PG, Nilsson L, Ardnor SN, et al. Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke. 2005;36(8):1661-5.
Wiklund, P. G., Nilsson, L., Ardnor, S. N., Eriksson, P., Johansson, L., Stegmayr, B., Hamsten, A., Holmberg, D., & Asplund, K. (2005). Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke, 36(8), 1661-5.
Wiklund PG, et al. Plasminogen Activator Inhibitor-1 4G/5G Polymorphism and Risk of Stroke: Replicated Findings in Two Nested Case-control Studies Based On Independent Cohorts. Stroke. 2005;36(8):1661-5. PubMed PMID: 16020771.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. AU - Wiklund,Per-Gunnar, AU - Nilsson,Lennart, AU - Ardnor,Sofie Nilsson, AU - Eriksson,Per, AU - Johansson,Lars, AU - Stegmayr,Birgitta, AU - Hamsten,Anders, AU - Holmberg,Dan, AU - Asplund,Kjell, Y1 - 2005/07/14/ PY - 2005/7/16/pubmed PY - 2005/12/13/medline PY - 2005/7/16/entrez SP - 1661 EP - 5 JF - Stroke JO - Stroke VL - 36 IS - 8 N2 - BACKGROUND AND PURPOSE: Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. METHODS: A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. CONCLUSIONS: Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction. SN - 1524-4628 UR - https://www.unboundmedicine.com/medline/citation/16020771/Plasminogen_activator_inhibitor_1_4G/5G_polymorphism_and_risk_of_stroke:_replicated_findings_in_two_nested_case_control_studies_based_on_independent_cohorts_ L2 - https://www.ahajournals.org/doi/10.1161/01.STR.0000174485.10277.24?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -