Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction

Boekholdt, S. Matthijs; Bijsterveld, Nick R.; Moons, A H M; Levi, Marcel; Büller, Harry R.; Peters, Ron J.G.

doi:10.1161/hc5001.100793

Cited by 180 publications

(144 citation statements)

References 58 publications

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“…Moreover, at least 37 separate studies have detected significant allelic dose-dependent correlations between carriage of the 4G allele and PAI1 protein levels in vivo, such that 4G4G homozygotes have the highest levels of circulating PAI1, 5G5G homozygotes have the lowest levels, and heterozygous individuals have intermediate levels of circulating PAI1 (Supplementary Table S1). Indeed, multiple studies and meta-analyses have found significant associations between 4G/5G genotypes and various vascular and thrombotic diseases (23)(24)(25)(26)(27)); yet, its role in cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of PAI1 in Invasive Breast Cancer: Evidence That Tumor-Specific Factors Are More Important Than Genetic Variation in Regulating PAI1 Expression

Sternlicht¹,

Dunning

Moore

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Plasminogen activator inhibitor-1 (PAI1) can promote cancer progression, and its protein expression in tumors is an independent indicator of poor prognosis in many forms of cancer. Here, we show that high PAI1 mRNA levels also predict for shorter overall survival in two independent breast cancer data sets, highlighting the importance of its transcriptional regulation. The −675insG (4G/5G) singlenucleotide polymorphism in the PAI1 gene promoter has been shown to influence PAI1 transcription, with the 4G allele eliciting higher reporter gene expression in vitro and higher levels of circulating PAI1 in vivo. Nevertheless, its genotypic distribution in 2,539 British women with invasive breast cancer was virtually identical to that seen in 1,832 matched controls (P = 0.72), and annual mortality rates for 4G4G, 4G5G, and 5G5G cases were 2.6%, 2.8%, and 3.1% per year, respectively (P = 0.10). Thus, there was no association with breast cancer incidence or outcome, and in a separate set of breast cancers, the 4G/5G single-nucleotide polymorphism showed no association with PAI1 mRNA expression (P = 0.85). By contrast, connective tissue growth factor (CTGF), which can regulate PAI1 expression in culture, was associated with PAI1 expression in three independent cohorts (P ≪ 0.0001). In addition, PAI1 gene copy number differences in the tumors were correlated with PAI1 mRNA expression (P = 0.0005) and seemed to affect expression independently of CTGF. Thus, local factors, such as CTGF and genomic amplification, seem to be more important than germ line genetic variation in influencing PAI1 expression and its untoward effects in breast cancer.Requests for reprints:

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Section: Introductionmentioning

confidence: 99%

Prognostic Value of PAI1 in Invasive Breast Cancer: Evidence That Tumor-Specific Factors Are More Important Than Genetic Variation in Regulating PAI1 Expression

Sternlicht¹,

Dunning

Moore

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…However, studies including different ethnic groups, such as Afro-Caribbeans, 7 Asians, 7 Pima Indians, 8 or Japanese, 9 have reported different frequencies of the 4G allele from those in non-Hispanic whites, as well as differences in the relation of the 4G/5G genotype to circulating levels of PAI-1. 8 The 4G/5G genotype has been related to the risk of myocardial infarction (reviewed in Boekholdt et al 10 ), sudden cardiac death, 11 transplant coronary artery disease, 12 and in-stent restenosis after coronary stent implantation. 13 These studies have focused on non-Hispanic whites.…”

mentioning

confidence: 99%

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

et al. 2003

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Background-The 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene has been related to cardiovascular disease. Methods and Results-Insulin resistance was measured with a frequently sampled intravenous glucose tolerance test in the Insulin Resistance Atherosclerosis Study (IRAS), and PAI-1 4G/5G promoter genotype was established by allelespecific polymerase chain reaction amplification of genomic DNA. There were 287 subjects with the 4G/4G genotype (18.4%), 691 heterozygote subjects (44.2%), and 586 carriers of the 5G/5G genotype (37.5%). The genotype distribution was different across the 3 ethnic groups (Pϭ0.001). PAI-1 levels were lower in blacks than in non-Hispanic whites and Hispanics and lower in non-Hispanic whites than in Hispanics (all Pϭ0.0001). Subjects homozygous for the 4G allele had the highest plasma PAI-1, heterozygote subjects were intermediate, and 5G homozygotes had the lowest levels of PAI-1. These patterns remained unaffected by adjustments for age, gender, clinical center, glucose tolerance status, body mass index, waist, triglycerides, and insulin resistance. Multiple linear regression analyses showed that the 4G/5G genotype explained very little of the variation in PAI-1 levels (0.63% in non-Hispanic whites, 0.99% in Hispanics, and 2.37% in blacks), and interaction analyses revealed no significant differences in the relation of circulating PAI-1 levels to the 4G/5G genotype by ethnicity (Pϭ0.4). Conclusions-We have shown ethnic differences in the PAI-1 4G/5G polymorphism along with corresponding differences in circulating PAI-1 levels. The association of the genotype with PAI-1 levels was seen consistently among all 3 ethnic groups and was unaffected by metabolic covariates, including insulin resistance. (Circulation. 2003;107:2422-2427.)

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“…Most polymorphisms of the coagulation system proteins involved with venous thrombosis present little or no association with an AMI 14 . In Brazil, Faria-Neto et al 15 demonstrated a low prevalence and no correlation of Factor V Leiden and prothrombin G20210A and methylenetetrahydrofolate redutase C677T (involved in…”

Section: Discussionmentioning

confidence: 98%

Infarto do miocárdio em atleta jovem associado ao uso de suplemento dietético rico em efedrina

Forte¹,

Precoma-Neto²,

Neto³

et al. 2006

Arq. Bras. Cardiol.

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Acute myocardial infarction, coronary disease, ephedrine. ischemia, infarction, and arrhythmias 5 .We report the case of a young athlete with no risk factors for cardiovascular disease who experienced a myocardial infarction during the period in which he used an ephedrinerich supplement. Case reportOur patient is a 28-year-old male, a mixed martial arts fighter, who for some time took Therma-Pro TM , a dietary supplement used in order to lose weight before weighing in for the fights. According to the patient, besides the weight loss (up to 12 kg in 20 days, when associated with intense physical training and diet), this product would cause palpitations, tremors, and insomnia. He had used the product before, and always experienced these symptoms. During the period of preparation for a wrestling match, the patient began using four tablets/day of Therma-Pro TM , and on the third day developed an intense resting chest pain, described as a tightening sensation, that worsened with effort and improved with rest, with prolonged intermittent duration. He sought medical help, and an analgesic was prescribed to no avail. After six days from the onset of pain, his condition progressed with syncope and hemiparesia on the right, and the patient was seen at other health care centers and referred to our institution merely 30 days after the onset of the clinical picture. On this occasion, that patient had already totally recovered from his motor deficit, but presented with congestive heart failure functional class II (NYHA). He reported no prior history of arterial hypertension, diabetes mellitus, dyslipidemia, or familial history of cardiovascular diseases. He had smoked half a pack of cigarettes a day for five years, but had stopped smoking 3 years prior. He was questioned directly about cocaine use on several occasions during his hospital stay; he denied use of illicit drugs and other stimulants, such as steroids and anabolic products.On physical examination his Blood pressure was 120/70 mmHg, Heart rate 72 bpm, weight 104 kg, and height, 1.77m. In spite of a body mass index in the obesity range (33.2), he had a large muscle mass and little adiposity.The test results showed an ECG with an extensive electrically Ephedrine is a sympathomimetic alkaloid derived from plants of the genus Ephedra, with more than 40 species distributed in areas of temperate and subtropical climates. For centuries, its use for therapeutic purposes has been disseminated among the Chinese who used the extract of the dehydrated plant (called Ma huang) to treat respiratory ailments 1 . In modern medicine, ephedrine has been used as a nasal decongestant, bronchodilator, and vasopressor 2 , but the therapeutic uses of these alkaloids have been restricted because of doubts as to their safety profile.Currently, dietary supplements that contain ephedrine and other ephedrine-related alkaloids are widely consumed in several countries for the purpose of energy enhancement (to increase athletic performance) and weight loss, in spite of clinical studies that show t...

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Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction

Cited by 180 publications

References 58 publications

Prognostic Value of PAI1 in Invasive Breast Cancer: Evidence That Tumor-Specific Factors Are More Important Than Genetic Variation in Regulating PAI1 Expression

Prognostic Value of PAI1 in Invasive Breast Cancer: Evidence That Tumor-Specific Factors Are More Important Than Genetic Variation in Regulating PAI1 Expression

Promoter (4G/5G) Plasminogen Activator Inhibitor-1 Genotype and Plasminogen Activator Inhibitor-1 Levels in Blacks, Hispanics, and Non-Hispanic Whites

Infarto do miocárdio em atleta jovem associado ao uso de suplemento dietético rico em efedrina

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