Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia.
It is known that the plasminogen activator inhibitor 1 (PAI-1) protein levels are increased in placentas of preeclamptic subjects. Therefore, we assessed whether polymorphisms related to the transcriptional control of the PAI-1 gene (-675 4G/5G and -844G/A) are associated with mild preeclampsia. We compared 52 women with preeclampsia to 80 women with a normal pregnancy. None of the preeclamptic women suffered from the severe form of preeclampsia. DNA was extracted from blood, and -675 4G/5G and -844G/A genotypes of the PAI-1 gene were determined. Since it has been shown that the presence of factor V Leiden, prothrombin G20210A, and MTHFR C677T gene variants may be associated with preeclampsia, their frequency was also evaluated in our study groups. The factor V Leiden, PT G20210A, and MTHFR C677T gene variants were not associated with preeclampsia. In the case of the -675 4G/5G polymorphism, genotypes 4G/4G and 5G/5G were more prevalent in the preeclamptic and in the control group, respectively. In the case of -844 G/A polymorphism, genotypes A/A and G/G were more prevalent in the preeclamptic and in the control group, respectively. By using the chi(2) test for trend, differences for both genotypes were significant (p = 0.0141 for the -675 genotypes and p = 0.0492 for the -844 genotypes). The frequency of the 4G and 5G alleles of the -675 gene polymorphism was significantly different between preeclamptic and normal women (p = 0.032). Differently, the allelic frequency of the -844 gene polymorphism did not show significant differences between preeclamptic and normal women (p = 0.083). In conclusion, the hypofibrinolytic genotypes 4G/4G and A/A at positions -675 and -844 of the PAI-1 gene are associated with the occurrence of mild preeclampsia independently of thrombophilic mutations of the factor V, prothrombin, and MTHFR genes.
Fabbro
Dora
D
Department of Biomedical Science and Technology, University of Udine, Udine General Hospital, Piazzale Kolbe 1, IT-33100 Udine, Italy.
D'Elia
Angela V
AV
Spizzo
Riccardo
R
Driul
Lorenza
L
Barillari
Giovanni
G
Di Loreto
Carla
C
Marchesoni
Diego
D
Damante
Giuseppe
G
D000328:Adult; D000483:Alleles; D005165:Factor V / Q000235:genetics; D005260:Female; D005342:Fibrinolysis; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009154:Mutation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D011516:Prothrombin / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)