Filimonović, Dejan

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Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population

Joksić, Ivana; Miković, Željko; Filimonović, Dejan; Munjas, Jelena; Karadžov-Orlić, Nataša; Egić, Amira; Joksić, Gordana

(Beograd : Društvo medicinskih biohemičara Srbije, 2020) 

TY  - JOUR
AU  - Joksić, Ivana
AU  - Miković, Željko
AU  - Filimonović, Dejan
AU  - Munjas, Jelena
AU  - Karadžov-Orlić, Nataša
AU  - Egić, Amira
AU  - Joksić, Gordana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3618
AB  - Background:Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one  of  the  causes  of  RPL.  Here  we  examined  the  prevalence  of  nine  thrombophilic  gene  polymorphisms  among women  with  history  of  recurrent  miscarriages  and  fertile controls.Methods:The study included 70 women with history of at least  three  early  pregnancy  losses  and  31  fertile  controls with  no  miscarriages.  We  investigated  mutations  in  genes responsible  for  clotting  and  fibrinolysis,  including  factor  V(FV) Leiden, FV H1299R, factor II (FII) G20210A, methyl-ene  tetrahydrofolate  reductase  (MTHFR)  C677T  and A1298C,  factor  XIII  (FXIII)  V34L,  plasminogen  activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor  (EPCR)  H1  and  H3  haplotypes  using  reverse  polymerase  chain  reaction  ViennaLab  cardiovascular  disease StrippAssays. Results:Our  results  showed  no  significant  increase  inprevalence  of  tested  polymorphisms  in  women  with  RPL. However, relative risk for PRL among women heterozygousfor FXIII V34L was 2.81 times increased (OR 2.81, 95% CI1.15–6.87,  P=0.023).  Haplotype  analysis  showed  that combined  presence  of  high-risk  genotypes  for  FXIII  andPAI-1  significantly  increases  risk  for  RPL  (OR  13.98,  CI95% 1.11–17.46, P=0.044).Conclusions:This  is  the  first  study  in  Serbian  population that investigated prevalence of FVR2, A1298C, FXIII V34Land  EPCR  gene  variants.  Compound  heterozygosity  forFXIII V34L and PAI-1 4G is significant risk factor for recur-rent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings.
AB  - Uvod: Ponavljani spontani pobačaji (PSP) su etiološki heterogeni i javljaju se kod 5% parova u reproduktivnom period. Jedan od mogućih uzroka PSP su i nasledne trombofilije. U okviru ove studije analizirali smo učestalost devet trombofilnih polimorfizama kod pacijentkinja sa ponavljanim spontanim pobačajima. Metode: Ispitanici su u studiji podeljeni u dve grupe na osnovu anamnestičkih podataka o broju spontanih pobačaja (70 u grupi sa PSP i 31 u kontrolnoj grupi). Ispitivani su sledeći genski polimorfizmi: faktor V Lajden (FVL), FVR2, faktor II (FII) G21210A, metilentetrahidrofolat reduktaza (MTHFR) C677T i A1298C polimorfizmi, inhibitor aktivatora plazminogena 1 (PAI-1) 4G/5G, faktor XIII (FXIII) V34L i endotelni protein C receptor (EPRC) H1, H2 i H3 haplotipovi. Za detekciju navedenih polimorfizama je korišćena metoda multipleks reakcije lančanog umnožavanja i reverzne hibridizacije na ViennaLab stripovima. Rezultati: Dobijeni rezultati nisu pokazali povećanu učestalost ispitivanih polimorfizama u grupi sa PSP. Posmatrajući uticaj pojedinačnih polimorfizama na ishod trudnoće pokazano je da polimorfizam FXIII V34L povećava rizik za ponavljane spontane pobačaje (OR 2,81, 95%CI 1,15-6,87, P=0,023). Analizom haplotipova ustanovljeno je da kombinovano prisustvo V34L i PAI-1 4G varijanti značajno povećava rizik za PSP (OR 13,98, CI 95% 1,11-17,46, P=0,044). Zaključak: Ovo je prva studija koja je ispitivala prevalencu FVR2, A1298C, FXIII V34L and EPCR polimorfizama u populaciji žena iz Srbije. Složeni heterozigoti za FXIII V34L i PAI-1 4G polimorfizme imaju značajno povišen rizik sa ponavljane gubitke trudnoće. Radi potvrde dobijenih rezultata potrebne su veće prospektivne studije.
PB  - Beograd : Društvo medicinskih biohemičara Srbije
T2  - Journal of Medical Biochemistry
T1  - Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population
T1  - Kombinovano prisustvo genskih polimorfizma faktora koagulacije XIII V34L i inhibitora plazminogen aktivatora 1 4G/5G značajno utiče na rizik od spontanog pobačaja u srpskoj populaciji
VL  - 39
IS  - 2
SP  - 199
EP  - 207
DO  - 10.2478/jomb-2019-0028
ER  - 
@article{
author = "Joksić, Ivana and Miković, Željko and Filimonović, Dejan and Munjas, Jelena and Karadžov-Orlić, Nataša and Egić, Amira and Joksić, Gordana",
year = "2020",
abstract = "Background:Recurrent pregnancy loss (RPL) is a heterogeneous condition affecting up to 5% of women of reproductive age. Inherited thrombophilia have been postulated as one  of  the  causes  of  RPL.  Here  we  examined  the  prevalence  of  nine  thrombophilic  gene  polymorphisms  among women  with  history  of  recurrent  miscarriages  and  fertile controls.Methods:The study included 70 women with history of at least  three  early  pregnancy  losses  and  31  fertile  controls with  no  miscarriages.  We  investigated  mutations  in  genes responsible  for  clotting  and  fibrinolysis,  including  factor  V(FV) Leiden, FV H1299R, factor II (FII) G20210A, methyl-ene  tetrahydrofolate  reductase  (MTHFR)  C677T  and A1298C,  factor  XIII  (FXIII)  V34L,  plasminogen  activator inhibitor-1 (PAI-1) 4G/5G and endothelial protein C receptor  (EPCR)  H1  and  H3  haplotypes  using  reverse  polymerase  chain  reaction  ViennaLab  cardiovascular  disease StrippAssays. Results:Our  results  showed  no  significant  increase  inprevalence  of  tested  polymorphisms  in  women  with  RPL. However, relative risk for PRL among women heterozygousfor FXIII V34L was 2.81 times increased (OR 2.81, 95% CI1.15–6.87,  P=0.023).  Haplotype  analysis  showed  that combined  presence  of  high-risk  genotypes  for  FXIII  andPAI-1  significantly  increases  risk  for  RPL  (OR  13.98,  CI95% 1.11–17.46, P=0.044).Conclusions:This  is  the  first  study  in  Serbian  population that investigated prevalence of FVR2, A1298C, FXIII V34Land  EPCR  gene  variants.  Compound  heterozygosity  forFXIII V34L and PAI-1 4G is significant risk factor for recur-rent miscarriage. Our results should be viewed in context of small case-control study, so further large prospective studies are need for confirmation of our findings., Uvod: Ponavljani spontani pobačaji (PSP) su etiološki heterogeni i javljaju se kod 5% parova u reproduktivnom period. Jedan od mogućih uzroka PSP su i nasledne trombofilije. U okviru ove studije analizirali smo učestalost devet trombofilnih polimorfizama kod pacijentkinja sa ponavljanim spontanim pobačajima. Metode: Ispitanici su u studiji podeljeni u dve grupe na osnovu anamnestičkih podataka o broju spontanih pobačaja (70 u grupi sa PSP i 31 u kontrolnoj grupi). Ispitivani su sledeći genski polimorfizmi: faktor V Lajden (FVL), FVR2, faktor II (FII) G21210A, metilentetrahidrofolat reduktaza (MTHFR) C677T i A1298C polimorfizmi, inhibitor aktivatora plazminogena 1 (PAI-1) 4G/5G, faktor XIII (FXIII) V34L i endotelni protein C receptor (EPRC) H1, H2 i H3 haplotipovi. Za detekciju navedenih polimorfizama je korišćena metoda multipleks reakcije lančanog umnožavanja i reverzne hibridizacije na ViennaLab stripovima. Rezultati: Dobijeni rezultati nisu pokazali povećanu učestalost ispitivanih polimorfizama u grupi sa PSP. Posmatrajući uticaj pojedinačnih polimorfizama na ishod trudnoće pokazano je da polimorfizam FXIII V34L povećava rizik za ponavljane spontane pobačaje (OR 2,81, 95%CI 1,15-6,87, P=0,023). Analizom haplotipova ustanovljeno je da kombinovano prisustvo V34L i PAI-1 4G varijanti značajno povećava rizik za PSP (OR 13,98, CI 95% 1,11-17,46, P=0,044). Zaključak: Ovo je prva studija koja je ispitivala prevalencu FVR2, A1298C, FXIII V34L and EPCR polimorfizama u populaciji žena iz Srbije. Složeni heterozigoti za FXIII V34L i PAI-1 4G polimorfizme imaju značajno povišen rizik sa ponavljane gubitke trudnoće. Radi potvrde dobijenih rezultata potrebne su veće prospektivne studije.",
publisher = "Beograd : Društvo medicinskih biohemičara Srbije",
journal = "Journal of Medical Biochemistry",
title = "Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population, Kombinovano prisustvo genskih polimorfizma faktora koagulacije XIII V34L i inhibitora plazminogen aktivatora 1 4G/5G značajno utiče na rizik od spontanog pobačaja u srpskoj populaciji",
volume = "39",
number = "2",
pages = "199-207",
doi = "10.2478/jomb-2019-0028"
}
Joksić, I., Miković, Ž., Filimonović, D., Munjas, J., Karadžov-Orlić, N., Egić, A.,& Joksić, G.. (2020). Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population. in Journal of Medical Biochemistry
Beograd : Društvo medicinskih biohemičara Srbije., 39(2), 199-207.
https://doi.org/10.2478/jomb-2019-0028
Joksić I, Miković Ž, Filimonović D, Munjas J, Karadžov-Orlić N, Egić A, Joksić G. Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population. in Journal of Medical Biochemistry. 2020;39(2):199-207.
doi:10.2478/jomb-2019-0028 .
Joksić, Ivana, Miković, Željko, Filimonović, Dejan, Munjas, Jelena, Karadžov-Orlić, Nataša, Egić, Amira, Joksić, Gordana, "Combined presence of coagulation factor XIII V34L and plasminogen activator inhibitor 1 4G/5G gene polymorphisms significantly contribute to recurrent pregnancy loss in serbian population" in Journal of Medical Biochemistry, 39, no. 2 (2020):199-207,
https://doi.org/10.2478/jomb-2019-0028 . .
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