title: Genetics of suspected thrombophilia in Serbian females with infertility, including three cases, homozygous for FII 20210A or FV 1691A mutations.
abstract: Reproductive failure (recurrent foetal loss, unexplained infertility and IVF implantation failure) may be, in a number of cases, explained by thrombophilia, either acquired or inherited. Several genes contribute to thrombophilia, some with major effect (Factor V, Factor II), and some with minor effect (MTHFR, PAI-1, ATIII, etc.). The aim of this study was to estimate frequency of thrombophilia-associated genotypes (FII20210G > A, FV1691G > A, MTHFR677C > T and PAI-1 -675 4G/5G) in a group of 1631 Serbian women experiencing reproductive failure, and compare it with a healthy, female control group. Our results showed marginally significant (p = 0.050) differences in allele frequencies between patients and controls for the FV1691 mutations. For the FII20210G > A, although the statistical significance was not achieved (p = 0.076), we found higher frequency of variant allele in patients compared to controls (1.87% vs. 0.38%, respectively) which may point to a possible role of this polymorphism in thrombotic events. For the MTHFR677C > T and PAI-1 -675 4G/5G, we found no difference in distributions of genotype or allele frequencies between these two groups (p > 0.05). For three subjects with very rare genotypes (two patients homozygous for FV1691G > A and one patient homozygous for FII20210G > A) we performed additional biochemical analyses for haemostasis, as well as genotyping of two polymorphisms (MTHFR1298A > C and ATIII786G > A).
authors.affiliation: a Institute of Forensic Medicine, Faculty of Medicine , University of Belgrade , Belgrade , Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Djurovic
authors.affiliation: a Institute of Forensic Medicine, Faculty of Medicine , University of Belgrade , Belgrade , Serbia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stojkovic
authors.affiliation: b Private Consulting Room "Thyreomedicus" , Belgrade , Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Todorovic
authors.affiliation: c Department of Oncology, Laboratory of Angiogenesis and Neurovascular Link , University of Leuven , Belgium.|d Laboratory of Angiogenesis and Neurovascular Link , Vesalius Research Center , Belgium.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Brajic
authors.affiliation: e Center for Medical Biochemistry , Clinical Center of Serbia , Belgrade , Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stankovic
authors.affiliation: f Institute for Laboratory Diagnostics Biomedica , Belgrade , Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Obradovic
authors.affiliation: g Institute of Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
authors.forename: Gorana
authors.initials: G
authors.lastname: Stamenkovic
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D009154:Mutation; D055771:Serbia; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics*
chemical_list: D001779:Blood Coagulation Factors
keywords: ATIII; FII 20210 G > A; FV leiden; Female infertility; MTHFR; PAI-1; homozygous mutation; inherited thrombophilia