Clinical InvestigationGeneticsPlasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke
Section snippets
Methods
The Health, Aging, and Body Composition (Health ABC) Study is a prospective, community-based study designed to investigate the effects of body composition on morbidity, functional limitations, and mortality. A total of 3075 participants were recruited from a random sample of white and all black Medicare beneficiaries residing within each zip code from the metropolitan areas surrounding Pittsburgh and Memphis from 1997 to 1998. Participants were eligible if they were 70 to 79 years of age;
Results
At baseline, the participants who developed myocardial infarction during the follow-up were more likely to be male, smokers and prevalent cases of coronary heart disease, stroke, and diabetes, reported less participation of physical activity, and had lower HDL cholesterol levels than those who did not develop myocardial infarction (Table I). In whites, those who developed myocardial infarction also had higher plasma PAI-1 levels. The participants who developed stroke were more likely to be
Discussion
This study, to our knowledge, is the first study on the association of common PAI-1 gene haplotypes with myocardial infarction and stroke. The common haplotypes containing the 4G allele were associated with higher PAI-1 levels overall and in whites. The pattern was similar in blacks, although the association was not statistically significant. However, neither PAI-1 gene polymorphisms nor common haplotypes were associated with the risk of either myocardial infarction or stroke.
In accordance with
References (26)
- et al.
Angiotensin I–converting enzyme and plasminogen activator inhibitor–1 gene variants: risk of mortality and fatal cardiovascular disease in an elderly population-based cohort
J Am Coll Cardiol
(1999) - et al.
Haplotype block structure and its applications to association studies: power and study designs
Am J Hum Genet
(2002) - et al.
A new statistical method for haplotype reconstruction from population data
Am J Hum Genet
(2001) - et al.
Phylogenetic relationships of the dwarf boas and a comparison of Bayesian and bootstrap measures of phylogenetic support
Mol Phylogenet Evol
(2002) - et al.
Plasminogen-activator inhibitor type 1 and coronary artery disease
N Engl J Med
(2000) - et al.
Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction
Proc Natl Acad Sci U S A
(1995) - et al.
The PAI-1 gene locus 4G/5G polymorphism is associated with a family history of coronary artery disease
Arterioscler Thromb Vasc Biol
(1998) - et al.
Plasminogen activator inhibitor–1 promoter 4G/5G genotype and plasma levels in relation to a history of myocardial infarction in patients characterized by coronary angiography
Arterioscler Thromb Vasc Biol
(1997) - et al.
The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor–1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Etude CasTemoins de I'nfarctus du Mycocarde
Thromb Haemost
(1995) - et al.
Promoter (4G/5G) plasminogen activator inhibitor–1 genotype and plasminogen activator inhibitor–1 levels in blacks, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study
Circulation
(2003)
Prediction of the risk of myocardial infarction from polymorphisms in candidate genes
N Engl J Med
Relationship between gene polymorphism of the PAI-1 promoter and myocardial infarction
Chin Med J (Engl)
PAI-1 4G/5G and ACE I/D gene polymorphisms and the occurrence of myocardial infarction in patients on intermittent dialysis
Nephrol Dial Transplant
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2023, Journal of Thrombosis and HaemostasisAssociation of G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms with susceptibility to myocardial infarction in Morocco
2016, Meta GeneCitation Excerpt :A single insertion/deletion of a “G” at position − 675 in the promoter region of the gene gives rise to 4G and 5G alleles, which differ by their regulation of PAI-1 activity (Nordt et al., 2001; Isordia-Salas et al., 2009). Numerous studies have found an association between SNPs in PAI-1 gene and the development of many diseases (HTA, stroke…); concerning (MI), results remain contradictory (Ding et al., 2006; Collet et al., 2003; Ye et al., 1995; Iacoviello et al., 1998; Nilsson et al., 2008). High plasma level of TG is also one of the important risk factors of cardiovascular diseases.
Genetic Susceptibility to Cardiovascular Diseases: From Mendelian Disorders to Common Variants
2016, Cardiovascular Diseases: Genetic Susceptibility, Environmental Factors and their InteractionCoronary thrombus in 34-year-old female patient with 4G/4G polymorphism in the PAI-1 gene
2016, Gynecologic Oncology ReportsCitation Excerpt :However, in that study, the PAI-1 polymorphism (4G) was not found associated with MI, whereas modest risk could not be excluded.13 While the mentioned data suggested positive association between the development of MI and PAI-1 gene polymorphism, Atherosclerosis, Thrombosis, and Vascular Biology Italian Study Group (2003), did not find any association between PAI-1 gene polymorphisms and the development of acute MI at a young age (under the age of 45 years).20 Ding et al. also found that PAI-1 gene polymorphisms were associated with high plasma PAI-1 levels, whereas they were not associated with MI or stroke.21
Genetics of ischaemic stroke in young adults
2015, BBA ClinicalCitation Excerpt :The human gene for PAI-1 (SERPINE1) is located on the long arm of chromosome 7. Several polymorphic loci have been described [80,96,98]; however, most of studies excluded an association between SERPINE1 variants and stroke [97,70]. MMPs regulate the accumulation of extracellular matrix during tissue injury through their protolytic activity and have an important role in vascular remodeling and development of atherosclerotic plaques [115,116].
Global fibrinolytic activity, PAI-1 level, and 4G/5G polymorphism in thai children with arterial ischemic stroke
2014, Journal of Stroke and Cerebrovascular Diseases
Support for this study was given by the Laboratory of Epidemiology, Demography and Biometry of the National Institute on Aging under National Institutes of Health's contract numbers N01-AG-6-2106, N01-AG-6-2102, and N01-AG-6-2103, and the Wake Forest University Claude D. Pepper Older Americans Independence Center (NIH P30-AG21332). In addition, Hologic Inc supported a validation study on body composition, but the investigators retained full independence in the conduct of this research.