The 4G/4G polymorphism of the hypofibrinolytic plasminogen activator inhibitor type 1 gene: An independent risk factor for serious pregnancy complications

Glueck, Charles J.; Phillips, Harvey; Cameron, Dan; Wang, Ping; Fontaine, R; Moore, Sarah K.; Sieve-Smith, Luann; Tracy, Trent

doi:10.1053/meta.2000.6749

Cited by 97 publications

(64 citation statements)

References 58 publications

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“…The difference was not statistically significant compared to controls (P=0.23), but it indicates that the PAI-1 4G/4G polymorphism might play a role in the pathogenesis of FL in the second trimester of pregnancy. This result is consistent with the study of Glueck et al (25) who reported that in a group of women homozygous for the PAI-1 4G allele, heritable hypo fibrinolysis was the major cause of prematurity (P=0.001) and second-and third-trimester fetal death (P=0.025). They also suggested that the 4G/4G genotype is associated with complications of pregnancy, probably by acting through thrombotic induction of placental insufficiency (25).…”

Section: Discussionsupporting

confidence: 93%

The Prevalence of Pai-1 4g/5g Polymorphism in Women With Fetal Loss – First Data for a Serbian Population / Učestalost Polimorfizma Pai-1 4g/5g Kod Žena Sa Spontanim Pobačajem - Prvi Podaci Za Srpsku Populaciju

Đorđević¹,

Gvozdenov²,

Pruner³

et al. 2013

Journal of Medical Biochemistry

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SummaryBackground: Plasminogen activator inhibitor 1 (PAI-1) is an inhibitor of fibrinolysis. The PAI-1 4G/5G polymorphism is associated with elevated plasma levels of PAI-1. Overexpression of PAI-1 and impaired fibrinolysis in homozygous carriers of the 4G/4G PAI polymorphism may lead to abnormal placental formation and increased risk of fetal loss (FL). The aim of our study was to determine the frequency of this polymorphism in patients with FL in a Serbian population. Methods: The study was carried out in a group of 203 women (91 controls and 112 women with FL). The presence of PAI-1 4G/5G polymorphism was detected by PCR-RFLP analysis. Results: Slightly increased frequency of the PAI-1 4G/4G genotype was observed in the study group compared to the controls (32.1% vs. 30.8%). The frequency of PAI-1 was highest in women experiencing FL in the second trimester of pregnancy (50%), but this difference was not statistically significant. Conclusions: Our findings suggest that PAI-1 4G/4G might be a risk factor for FL occurring in the second trimester of pregnancy. Further studies are required in order to determine the role of PAI-1 4G/5G polymorphism in the etiology of FL.

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Section: Discussionsupporting

confidence: 93%

The Prevalence of Pai-1 4g/5g Polymorphism in Women With Fetal Loss – First Data for a Serbian Population / Učestalost Polimorfizma Pai-1 4g/5g Kod Žena Sa Spontanim Pobačajem - Prvi Podaci Za Srpsku Populaciju

Đorđević¹,

Gvozdenov²,

Pruner³

et al. 2013

Journal of Medical Biochemistry

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“…Recent researches had showed that heterozygosity and homozygosity for the 4G polymorphism of the PAI-1 gene is consistently associated with increased PAI-1 activity levels [31]. This genotype is much more common in women with PCOS [31]. Plasma PAI-1 antigen concentrations and PAI-1 activity were increased in our lean patients with PCOS and fasting insulin concentrations as well as insulin resistance indices were directly related to PAI-1 concentrations and activity.…”

Section: Discussionmentioning

confidence: 53%

“…It has previously determined that major factor influencing PAI-1 concentration in women was insulin resistance [17,[28][29][30]. Recent researches had showed that heterozygosity and homozygosity for the 4G polymorphism of the PAI-1 gene is consistently associated with increased PAI-1 activity levels [31]. This genotype is much more common in women with PCOS [31].…”

Section: Discussionmentioning

confidence: 99%

The Plasminogen Activator System in Young and Lean Women with Polycystic Ovary Syndrome

et al. 2004

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Abstract. The purpose of the study was to evaluate the plasminogen activator inhibitor-1 (PAI-1) levels and PAI-1 activity in young and lean women with PCOS and to compare with controls matched for age and weight. Thirty two women with PCOS and 25 weight and age-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound and fasting blood samples were taken for hematological and biochemical tests. Fasting insulin, glucose, lipid profile, FSH, LH, PRL, testosterone, SHBG, 17-hydroxyprogesterone, androstenedione, PAI-1 antigen; PAI-1 activity, insulin sensitivity indices (HOMA and QUICKI) were measured. PAI-1 Ag and activity were significantly higher in PCOS women than healthy control group. PAI-1 levels were directly correlated with BMI, insulin levels and insulin sensitivity indices. PAI-1 activity was also correlated with insulin levels and insulin resistance. As a conclusion PAI-1 Ag levels and activity were increased in lean PCOS women and these were directly correlated with insulin resistance. The finding may contribute to evidence of increase risk of cardiovascular disease and anovulatory infertility in PCOS women. Plasminogen activator inhibitor-1 (PAI-1) is a 52 kD glycoprotein whose main role is in the inhibition of plasmin formation during plasminogen activation and fibrinolysis [9]. The relationship between PAI-1 levels and cardiovascular risk is not clear [10,11]. Moreover, some studies speculated that overproduction of PAI-1 leads to distortions in the ovarian plasminogenplasmin pathway and anovulation in women with PCOS [12,13]. PAI-1 levels and metabolic parameters that can affect the PAI-1 concentrations in women with PCOS are still under debate. Insulin resistance is found in women with PCOS independent of body mass index (BMI) [14]. In diabetic patients, insulin resistance correlated linearly with plasma concentrations of PAI-1 [15,16]. Elevated PAI-1 levels have been demonstrated in some studies of women with PCOS [13,17,18]. Therefore it has been suggested that insulin mediated elevation of PAI-1 may contribute to anovulatory infertility and increased risk of cardiovascular disease those were determined in women with PCOS. However most of these studies included obese or over-weight patient and control groups, so it was not clear from these studies whether the finding of raised PAI-1 levels in women with PCOS was independent of obesity or not. The present study was designed to evaluate PAI-1 levels and activity in young and lean women with PCOS and compare with

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“…In other studies of women with PCOS, we have previously shown that the 4G4G PAI-1 mutation [19] was an independent determinant of serious pregnancy complications and that PAI-1 activity was an independent determinant of miscarriage [20][21][22][23] and recurrent pregnancy loss [24]. Elevated levels of PAI-1 have been associated with increased cardiovascular risk and increased thrombogenic tendency [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

4G/5G Polymorphism of PAI-1 gene and Alu-repeat I/D polymorphism of TPA gene in Turkish patients with polycystic ovary syndrome

Karadeniz

Erdoğan

Berdelı

et al. 2007

J Assist Reprod Genet

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Purpose Polycystic ovary syndrome (PCOS) is one of the most encountered endocrine malfunctions. PCOS patients have enhanced activation of the blood coagulation system. Methods Eighty-six young women with PCOS and 70 healthy control women were included in our study. PCOS patients and controls were matched for age, body mass index, and allele frequency. Genetic analysis of TPAI and PAI-1 were performed in all subjects. Results and conclusions No statistically significant differences have been detected about the ratios of genotypes resulting from PAI-1 promotor 4G/5G gene polymorphism. PAI-1 765 4G/5G gene polymorphism and TPA gene's Alurepeat insertion/deletion (I/D) polymorphism ratios were not different from the controls. In this study it is shown by the analysis of TPA gene's Alu-repeat insertion/deletion (I/D) polymorphism the PCOS patients with genotype II had lowers total cholesterol and LDL-cholesterol levels.

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The 4G/4G polymorphism of the hypofibrinolytic plasminogen activator inhibitor type 1 gene: An independent risk factor for serious pregnancy complications

Cited by 97 publications

References 58 publications

The Prevalence of Pai-1 4g/5g Polymorphism in Women With Fetal Loss – First Data for a Serbian Population / Učestalost Polimorfizma Pai-1 4g/5g Kod Žena Sa Spontanim Pobačajem - Prvi Podaci Za Srpsku Populaciju

The Prevalence of Pai-1 4g/5g Polymorphism in Women With Fetal Loss – First Data for a Serbian Population / Učestalost Polimorfizma Pai-1 4g/5g Kod Žena Sa Spontanim Pobačajem - Prvi Podaci Za Srpsku Populaciju

The Plasminogen Activator System in Young and Lean Women with Polycystic Ovary Syndrome

4G/5G Polymorphism of PAI-1 gene and Alu-repeat I/D polymorphism of TPA gene in Turkish patients with polycystic ovary syndrome

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