50 research outputs found
Functional analysis of FIIc.1787G>A (protrombin, Belgrade) and FIIc.*64_*66del gene variants and their assotiation with trombophilia
Protrombin predstavlja zimogen trombina (koagulacinog faktora II), koji ima
centralnu ulogu u održanju hemostazne ravnoteže. Zahvaljujući alosteričnoj regulaciji,
trombin može da vrši i prokoagulantnu i antikoagulantnu funkciju. Region 3' kraja gena
za protrombin ima nekanonsku organizaciju i podložan je nastanku genskih varijanti
koje mogu imati značajnu ulogu u regulaciji ekspresije i funkcije protrombina. Do sada
opisane varijante u ovom regionu su povezivane sa povišenom ekspresijom protrombina
koja može dovesti do hiperkoagulacije i povećane sklonosti ka trombozama, odnosno
trombofiliji.
U Laboratoriji za molekularnu biologiju, Instituta za molekularnu genetiku i
genetičko inženjerstvo, u 3' kraju gena za protrombin opisane su FIIc.1787G>A i
FIIc.*64_*66del varijante čiji mehanizmi do sada nisu rasvetljeni. Varijanta
FIIc.1787G>A (protrombin Beograd) se nalazi u poslednjem egzonu gena za
protrombin i dovodi do aminokiselinske zamene Arg596Gln u proteinu. Ova varijanta
se nalazi u regionu za koji se vezuju joni natrijuma, neophodni za prokoagulantnu
aktivnost trombina, kao i prirodni trombinski inhibitor- antitrombin. Varijanta
FIIc.*64_*66del se nalazi u 3' netranslatirajućem regionu gena i predstavlja deleciju 3
nukleotida. Imajući u vidu pozicije u različitim strukturnim elementima 3' kraja gena,
pretpostavlja se da su mehanizmi delovanja ovih varijanti različiti.
Prvi deo studije je imao za cilj određivanje učestalosti FIIc.1787G>A i
FIIc.*64_*66del varijanti kod 353 pacijenta sa različitim trombotičkim poremećajima i
250 zdravih ispitanika u srpskoj populaciji. Pacijenti su u zavisnosti od tipa
trombotičkog poremećaja podeljeni u 4 grupe: tromboze dubokih vena (94 pacijenta),
izolovani plućni embolizam (104 pacijenta), kombinovani trombotički poremećaji (49
pacijenata) i spontani pobačaji (106 pacijentkinja).
Drugi deo studije je obuhvatio ex vivo analize, s ciljem da se ispita uticaj
navedenih varijanti na funkcionalnost i raspoloživu količinu protrombina u plazmi
ispitanika...Prothrombin is a zymogen of thrombin (coagulation factor II), which plays a
central role in maintaining hemostatic balance. Due to the allosteric regulation,
thrombin has dual function: procoagulant and anticoagulant. The 3' end of prothrombin
gene has noncanonical organization, which is susceptible to the genetic variants that
might have a significant role in the regulation of prothrombin expression and function.
Variants reported within this region lead to increased prothrombin expression which is
associated with hypercoagulability and increased tendency to thrombophilia.
In the Laboratory for Molecular Biology at the Institute of Molecular Genetics
and Genetic Engineering, we have reported FIIc.1787G>A and FIIc.*64_*66del
variants in 3' end of prothrombin gene, but their mechanisms of action have not been
elucidated so far. The FIIc.1787G>A (prothrombin Belgrade) is located in the last exon
of the prothrombin gene, leading to amino acid substitution Arg596Gln in the protein.
This variant is positioned in a region of antithrombin (thrombin inhibitor) binding site,
as well as in Na+ binding loop, which is significant for procoagulant activity of
thrombin. The FIIc.*64_*66del is located in the 3' untranslated gene region and
represents a deletion of three nucleotides. Taking into account the position of these two
variants in different structural elements of 3' end of prothrombin gene, it is assumed that
they differ in the mechanisms of action.
In the first part of the study, we determined the frequency of FIIc.1787G>A and
FIIc.*64_*66del variants in 353 patients with thrombotic disorders and 250 healthy
subjects in Serbian population. Patients were divided into 4 groups according to the type
of thrombotic disorders: deep vein thrombosis (94 patients), isolated pulmonary
embolism (104 patients), combined thrombotic disorders (49 patients) and fetal loss
(106 patients).
The second part of the study included the ex vivo analyses, with aim to
investigate the impact of these variants on the functionality and available amount of
prothrombin in the subjects plasma samples..
Functional analysis of FIIc.1787G>A (protrombin, Belgrade) and FIIc.*64_*66del gene variants and their assotiation with trombophilia
Protrombin predstavlja zimogen trombina (koagulacinog faktora II), koji ima
centralnu ulogu u održanju hemostazne ravnoteže. Zahvaljujući alosteričnoj regulaciji,
trombin može da vrši i prokoagulantnu i antikoagulantnu funkciju. Region 3' kraja gena
za protrombin ima nekanonsku organizaciju i podložan je nastanku genskih varijanti
koje mogu imati značajnu ulogu u regulaciji ekspresije i funkcije protrombina. Do sada
opisane varijante u ovom regionu su povezivane sa povišenom ekspresijom protrombina
koja može dovesti do hiperkoagulacije i povećane sklonosti ka trombozama, odnosno
trombofiliji.
U Laboratoriji za molekularnu biologiju, Instituta za molekularnu genetiku i
genetičko inženjerstvo, u 3' kraju gena za protrombin opisane su FIIc.1787G>A i
FIIc.*64_*66del varijante čiji mehanizmi do sada nisu rasvetljeni. Varijanta
FIIc.1787G>A (protrombin Beograd) se nalazi u poslednjem egzonu gena za
protrombin i dovodi do aminokiselinske zamene Arg596Gln u proteinu. Ova varijanta
se nalazi u regionu za koji se vezuju joni natrijuma, neophodni za prokoagulantnu
aktivnost trombina, kao i prirodni trombinski inhibitor- antitrombin. Varijanta
FIIc.*64_*66del se nalazi u 3' netranslatirajućem regionu gena i predstavlja deleciju 3
nukleotida. Imajući u vidu pozicije u različitim strukturnim elementima 3' kraja gena,
pretpostavlja se da su mehanizmi delovanja ovih varijanti različiti.
Prvi deo studije je imao za cilj određivanje učestalosti FIIc.1787G>A i
FIIc.*64_*66del varijanti kod 353 pacijenta sa različitim trombotičkim poremećajima i
250 zdravih ispitanika u srpskoj populaciji. Pacijenti su u zavisnosti od tipa
trombotičkog poremećaja podeljeni u 4 grupe: tromboze dubokih vena (94 pacijenta),
izolovani plućni embolizam (104 pacijenta), kombinovani trombotički poremećaji (49
pacijenata) i spontani pobačaji (106 pacijentkinja).
Drugi deo studije je obuhvatio ex vivo analize, s ciljem da se ispita uticaj
navedenih varijanti na funkcionalnost i raspoloživu količinu protrombina u plazmi
ispitanika...Prothrombin is a zymogen of thrombin (coagulation factor II), which plays a
central role in maintaining hemostatic balance. Due to the allosteric regulation,
thrombin has dual function: procoagulant and anticoagulant. The 3' end of prothrombin
gene has noncanonical organization, which is susceptible to the genetic variants that
might have a significant role in the regulation of prothrombin expression and function.
Variants reported within this region lead to increased prothrombin expression which is
associated with hypercoagulability and increased tendency to thrombophilia.
In the Laboratory for Molecular Biology at the Institute of Molecular Genetics
and Genetic Engineering, we have reported FIIc.1787G>A and FIIc.*64_*66del
variants in 3' end of prothrombin gene, but their mechanisms of action have not been
elucidated so far. The FIIc.1787G>A (prothrombin Belgrade) is located in the last exon
of the prothrombin gene, leading to amino acid substitution Arg596Gln in the protein.
This variant is positioned in a region of antithrombin (thrombin inhibitor) binding site,
as well as in Na+ binding loop, which is significant for procoagulant activity of
thrombin. The FIIc.*64_*66del is located in the 3' untranslated gene region and
represents a deletion of three nucleotides. Taking into account the position of these two
variants in different structural elements of 3' end of prothrombin gene, it is assumed that
they differ in the mechanisms of action.
In the first part of the study, we determined the frequency of FIIc.1787G>A and
FIIc.*64_*66del variants in 353 patients with thrombotic disorders and 250 healthy
subjects in Serbian population. Patients were divided into 4 groups according to the type
of thrombotic disorders: deep vein thrombosis (94 patients), isolated pulmonary
embolism (104 patients), combined thrombotic disorders (49 patients) and fetal loss
(106 patients).
The second part of the study included the ex vivo analyses, with aim to
investigate the impact of these variants on the functionality and available amount of
prothrombin in the subjects plasma samples..
Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
Introduction. Ischemic stroke (IS) is a heterogeneous dis-order caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with IS, especially in patients with early onset of IS. Case report. We describe a case of a young adult male who developed an unprovoked IS. Biochemical, immunological, and thrombophilia screening, as well as DNA sequencing, were performed in order to reveal molecular pathology underlying the stroke of the patient. Thrombophilia testing showed that patient was a homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of the recently reported F2 c.1824C>T gene variant, located in the last exon of the pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, hypofibrinolysis, and altered fibrin clot phenotype. Conclusion. Our results suggest that the newly reported F2 c.1824C>T gene variant might have a synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in the formation of altered fibrin clot phenotype characterized by thin, densely packed fibrin fibers, which makes clot less susceptible to fibrinolysis and greatly in-creases the risk for early ischemic stroke onset.Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu
The prevalence of PAI-1 4G/5G gene variant in Serbian population
Uvod: Inhibitor aktivatora plazminogena 1 (PAI-1) ima značajnu ulogu u procesu inhibicije fibrinolize i normalne hemostaze. Prisustvo PAI-1 4G/4G genotipa uzrokuje povećanje ekspresije PAI-1. Povišen nivo PAI-1 u krvi povezan je sa brojnim bolestima kao što su tromboza, moždani udar, infarkt miokarda, spontani pobačaji, preeklampsija, insulinska rezistencija, dijabetes tipa 2, rak dojke i astma. U okviru ove studije određivana je učestalost PAI-1 4G/5G genske varijante kod zdravih ispitanika u srpskoj populaciji. Metode: Studija je obuhvatala grupu od 210 zdravih ispitanika (105 žena i 105 muškaraca). Prisustvo PAI-1 4G/5G genske varijante detektovano je PCR-RFLP metodom. Rezultati: Učestalost PAI-1 4G/4G genotipa iznosila je 34,76% i bila je povećana u odnosu na PAI-1 5G/5G genotip (19,05%), dok je najzastupljeniji genotip bio PAI-1 4G/5G (46,19%). Učestalost 4G alela bila je viša (0,58) u odnosu na 5G alel (0,42). Zaključci: Učestalost PAI-1 4G/5G genske varijante u srpskoj populaciji slična je sa okolnim populacijama. Rezultati ove studije su značajni, jer predstavljaju prve podatke za srpsku populaciju što će omogućiti dalja istraživanja o ulozi PAI-1 4G/5G genske varijante u patogenezi brojnih bolesti.Introduction: Plasminogen activator inhibitor 1 (PAI-1) has a major role in inhibition of firinolysis and normal haemostasis. The presence of the PAI-1 4G/4G genotype leads to increased expression of PAI-1. High blood level of PAI-1 is associated with many diseases such as thrombosis, cerebral insult, myocardial infarction, pregnancy loss, preeclampsia, insulin resistance, type 2 diabetes, breast cancer and asthma. In this study, the prevalence of PAI-1 4G/5G gene variant was determined in healthy subjects from Serbian population. Methods: The study was carried out in a group of 210 healthy subjects (105 women and 105 men). The presence of PAI-1 4G/5G gene variant was detected by PCR-RFLP analysis. Results: The prevalence of PAI-1 4G/4G genotype was 34.76% and it was increased compared to PAI-1 5G/5G genotype (19.05%). The most frequent was PAI-1 4G/5G genotype (46.19%). Allelic frequency for 4G allele was higher (0.58) compared to 5G allele (0.42). Conclusions: The prevalence of PAI-1 4G/5G gene variant in Serbian population is similar to the neighboring populations. Results of this study represent the first data for Serbian population. This study could be useful for further research where the role of PAI-1 4G/5G gene variant will be assessed in the pathogenesis of many diseases
Uticaj DOAK i DOAC-REMOVE® na testove koagulacije u toku testiranja trombofilije kod bolesnika lečenih primenom DOAK
Background/Aim. Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove® on coagulation assays dur-ing thrombophilia testing. Methods. The study was car-ried out from January 2019 to the end of June 2020. It in-cluded 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove® tablets (activated charcoal). The results before and after DOAC-Remove® were compared. Results. Posi-tive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove®, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove®, the activated pro-tein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove®, the APC-R was measurable in all cases. Comparing the results obtained from the sam-ples before and after DOAC-Remove®, a difference was noted in relation to all dilute Russell's viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were prac-tically inactivated after the addition of the DOAC-Remove®, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant re-sults.Uvod/Cilj. Primena direktnih oralnih antikoagulansa (DOAK)
značajno utiče na testove koagulacije. Cilj rada bio je da se pro-
ceni uticaj DOAK i DOAC-Remove® tableta (aktivni ugalj) na
testove koagulacije tokom ispitivanja trombofilije. Metode.
Istraživanjem, sprovedenim od januara 2019. do juna 2020.
godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om i
testiranih na trombofiliju zbog venskog tromboembolzma
(VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63
godine (medijana 47,6 godina). Ispitivanje trombofilije izvršeno
je upotrebom DOAC-Remove® tableta (aktivni ugalj).
Upoređivani su rezultati pre i posle primene DOAC-Remove®.
Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) test
dobijeni su kod 20% bolesnika lečenih apiksabanom, kod
100% bolesnika lečenih dabigatranom i kod 70% lečenih riva-
roksabanom, a u uzorcima posle DOAC-Remove® pozitivnost
na LA dobijena je samo kod jednog bolesnika iz grupe lečnih
apiksabanom. Pre primene DOAC-Remove®, rezistencija na
aktivisani protein C (activated protein C resistance – APC-R) bila je
merljiva kod 40% i 80% bolesnika lečenih dabigatranom, od-
nosno rivaroksabanom, dok je posle primene DOAC-
Remove®, APC-R bila merljiva u svim slučajevima.
Upoređivanjem rezultata dobijenih iz uzoraka pre i posle
primene DOAC-Remove®, primećena je razlika u odnosu na
sve testove vremena koagulacije izvršene razblaženim Russell-
ovim zmijskim otrovom (dilute Russell’s viper venom time –
dRVVT), osim dRVVT u grupi bolesnika lečenih apiksabanom.
Na koagulacionu metodu za otkrivanje APC-R značajno je uti-
cao dabigatran, a manje rivaroksaban. Zaključak. Nakon
primene DOAC-Remove® tableta, DOAK su praktično
inaktivisani što je omogućilo izvođenje analiza za LA i APC-R i
dobijanje relevantnih rezultata testova
The c20068t gene variant in the 3 ' end of the prothrombin gene and recurrent pregnancy loss: a pilot study
Recurrent pregnancy loss (RPL) is a health problem affecting up to 5% of women of reproductive age. Several thrombophilic risk factors might contribute to RPL. To investigate relationship between a novel C20068T gene variant in the 3' end of prothrombin gene and RPL, we tested 153 women with RPL and 111 controls for the presence of this gene variant. In patients, we have detected four heterozygous (2.61%) and no homozygous carriers. In controls, no carriers were detected. Our results indicate higher prevalence of C20068T gene variant in women with RPL but this difference was not statistically significant. However, in patients who suffered 5 or more RPL, frequency of C20068T gene variant was significantly increased compared to controls (12.5% vs. 0%, P = 0.02). This is the first study which points out a possible role of C20068T gene variant in etiology of RPL, but larger studies should be carried out to confirm our findings
The 3 ' End Prothrombin Gene Variants in Patients With Different Thrombotic Events
Background: Prothrombin (FII) A19911G and C20221T gene variants are associated with increased prothrombin levels and potentially represent thrombotic risk factors. Objective: To determine the frequency of A19911G and C20221T FII gene variants in patients with thrombotic disorders and in women who have experienced pregnancy loss (PL). Methods: We determined the frequency of these variants in 133 patients with deep venous thrombosis (DVT), 80 patients with isolated pulmonary embolism (PE), 101 patients with idiopathic PL, and 180 control individuals. Results: The FII A19911G variant was more prevalent in patients with DVT and with PL compared with controls; however, these differences were not statistically significant. The 19911GG genotype was associated with increased risk of PE (odds ratio, 1.91; 95% confidence interval, 1.04-3.51). We did not detect carriers of the FII C20221T gene variant in this study. Conclusions: This is the first study, to our knowledge, that demonstrates the FII 1991199 genotype may represent a risk factor for isolated PE. Also, our results show that the FII C20221T is a rare variant in this population and therefore, routine thrombophilia screening should not include screening for this genotype
The effect of prothrombin, the precursor of thrombin, on the proliferation and migration of colorectal cancer cells
Thrombotic disorders are some of the main comorbidities in cancer patients. So far, research has indicated that thrombin, a key regulator of hemostasis, contributes to cancer progression. However, data on its origin in tumor microenvironments remain elusive. Based on previous research, we analyzed the RNA and protein expression of prothrombin, a precursor of thrombin, in selected colorectal cancer (CRC) cell lines. Since the effect of prothrombin in cancer development has not been previously reported, we treated the cells for 24 h and 48 h with different prothrombin concentrations and assessed the effect on cell proliferation and migration. Our results show that the tested CRC cell lines expressed prothrombin and that prothrombin inhibited proliferation and migration. The presented results suggest that prothrombin may contribute to CRC etiopathology and could serve as a potential diagnostic biomarker and therapeutic target. The mechanisms underlying prothrombin expression in cancer cells, potential prothrombin activation, and the underlying processes driving the described effects warrant further investigation
Inherited thrombophilic risk factors in Serbian breast cancer patients
Breast cancer is the leading cause of cancer-related death among women. An increased burden of thrombotic events among breast cancer patients, leading to higher mortality and morbidity rates, is well established. There are a number of genetic risk factors associated with thrombosis, but their contribution to thrombotic tendencies in patients with cancer is not completely elucidated. We aimed to investigate possible role of FV Leiden, FII G20210A, MTHFR C677T and PAI-1 4G/5G gene variants in etiopathology of breast cancer and accompanying thrombosis in cohort of Serbian patients. Our study included 316 subject divided in three groups: breast cancer patients with (97) or without (99) accompanying thrombosis and healthy control group (120). According to our results, the prevalence for all four prothrombotic gene variants were similar in cancer patients with and without thrombosis and no statistically significant difference was observed between these groups. We detected lower frequency of MTHFR 677TT genotype in breast cancer patients when compared to control group (P=0.014; OR=0.145 (95%CI 0.031-0.679)), indicated that MTHFR C677T homozygosity could play a protective role in breast cancer susceptibility. Our study noted the lack of association between common prothrombotic gene variants and increased prothrombotic risk in Serbian breast cancer patients. Also, our results point out possible role of MTHFR 677TT genotype in etiology of breast cancer, but further studies on larger cohort of patients are needed
The prevalence of PAI-1 4G/5G polymorphism in women with fetal loss: First data for a Serbian population
Uvod: Inhibitor aktivatora plazminogena 1 (PAI-1) igra značajnu ulogu u procesu inhibicije fibrinolize. Pokazano je da je PAI-1 4G/5G polimorfizam povezan sa povišenim nivoom PAI-1 proteina u plazmi. Povećana ekspresija PAI-1 i smanjena fibrinoliza kod homozigotnih nosilaca PAI-1 4G/5G polimorfizma može dovesti do poremećaja tokom formiranja placente i povećanja rizika za spontane pobačaje (SP). U okviru ove studije analizirali smo učestalost PAI-1 4G/5G polimorfizma kod pacijentkinja sa spontanim pobačajima. Metode: Studija je obuhvatila grupu od 203 žene (91 u kontrolnoj grupi i 112 žena sa SP). Prisustvo PAI-1 4G/5G polimorfizama je detektovano PCR-RFLP analizom. Rezultati: Detektovana učestalost homozigotnih nosilaca PAI-1 4G/5G polimorfizma je bila nešto visa u grupi pacijentkinja u odnosu na kontrolnu grupu (32,1% vs. 30,8%). Najviša učestalost je detektovana kod žena koje su imale SP u drugom trimestru trudnoće (50%), ali ova razlika nije bila statistički značajna. Zaključak Rezultati naše studije ukazuju da PAI-1 4G/4G može biti faktor rizika za pojavu SP u drugom trimestru trudnoće. Potrebna su dalja ispitivanja u cilju određivanja uloge PAI-1 4G/4G polimorfizma u etiologiji spontanih pobačaja.Background: 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