• Reproductive disorders associated with genetically determined tendency to hypercoagulability 
To content

Reproductive disorders associated with genetically determined tendency to hypercoagulability 

HEALTH OF WOMAN.2015.7(103):130–133; doi 10.15574/HW.2015.103.130 
 

Reproductive disorders associated with genetically determined tendency to hypercoagulability 
 

Veropotvelyan N. P., Pogulyay Y. S., Klimenko S. V., Arbuzova S. B.

«Inter-provincial center of medical genetics and prenatal diagnosis», Krivoy Rog

Institute of experimental radiology of the State establishment «National scientific center»

Donetsk specialized center of medical genetics and prenatal diagnosis, Mariupol 
 

A study to determine the SNP’s in genes associated with susceptibility to blood clots and abnormal folate metabolism (FGB G455A, FII G20210A, FV 1691A, PAI-1 5G/4G, MTHFR C677T, MTR A2756G) in groups of women with early pregnancy losses episodes (n=781) and women who had a history of one or more episodes of placental /chorion abruption, stillbirth or antenatal fetal death (n=59) were conducted..

Analysis of the survey results showed that the genotype frequency FII G/A group of early miscarriage is 4 times higher than population prevalence of mutations G20210A FII (5.8% vs. 1.4%; p <0.05); frequency of genotype G/A FV group of miscarriage is 2.2 times lower than this mutation prevalence; combination heterozygous genotype C/T 677 MTHFR + A/G 2756 MTR significantly to 2.98 times more common in the group of women with multiple episodes of early abortion (20.56% vs. 6.9%; р<0.01); genotype FGB A/A 455 at 4.66 times significantly more common in placental /chorion abruption (77.78% versus 21.7%; р<0.01); associative links with the pregnancy losses and the polymorphic variant gene PAI-1 could not be found. 
 

Key words: hereditary thromobophilia, miscarriage, placental abruption. 
 

REFERENCES

1. Simpson JL, Carson SA. 2013. Genetic and nongenetic causes of pregnancy loss. Glob. libr. women’s med. (ISSN: 1756-2228). DOI10. 3843/ GLOWM. 10319

2. Regan L, Braude PR, Trembath PL: 1989. Influence of postreproductive performance on risk of spontaneous abortion. Br Med J 299:551. http://dx.doi.org/10.1136/bmj.299.6698.541

3. Based on data from Warburton D, Fraser FC. 1964. Spontaneous abortion risks in man. Am J Hum Genet 16:1. Poland BJ, Miller JP, Jones DC et al. 1977. Reproductive counseling in patients who had a spontaneous abortion. Am J Obstet Gynecol 127:685. Regan L: A prospective study on early abortion. In Beard RW, Sharp F eds: Early Pregnancy Loss: Mechanisms and Treatment:22. London, Royal College of Obstetricians and Gynaecologists. 1988.

4. Preston FE, Rosendaal FR, Walker ID, Briet E, Berntorp E, Conard J, Fontcuberta J, Makris M, Mariani G, Noteboom W, Pabinger I, Legnani C, Scharrer I, Schulman S. & van der Meer, F.J.M. 1996. Increased fetal loss in women with heritable thrombophilia. The Lancet 348:913–916. http://dx.doi.org/10.1016/S0140-6736(96)04125-6

5. Rey E, Kahn SR, David M et al. 2003. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 361:901. http://dx.doi.org/10.1016/S0140-6736(03)12771-7

6. Kovalesky G, Gracia CR, Berlin JA et al. 2004. Evaluation of the association between hereditary thromphilias and recurrent pregnancy loss. Arch Intern Med 164:558. http://dx.doi.org/10.1001/archinte.164.5.558; PMid:15006834

7. Sarah A. Bennett, Catherine N. 2012. Bagot and Roopen Arya. Pregnancy loss and thrombophilia: the elusive link British Journal of Haematology 157:529–542. http://dx.doi.org/10.1111/j.1365-2141.2012.09112.x; PMid:22449204

8. Greer I. 2003. Thrombophilia: implications forpregnancy outcome. Thrombosis Research 109:73–81. http://dx.doi.org/10.1016/S0049-3848(03)00095-1

9. Макух ГВ. 2012. Автореферат дисертації на здобуття наукового ступеня доктора біологічних наук. Мутації, що успадковуються як генетичний тягар: частота, фенотипові асоціації, діагностика. Київ.

10. Spector EB. 2005, Jul-Aug. 7. Technical standards and guidelines: venous thromboembolism (Factor V=Leiden and prothrombin 20210G > A testing): a disease-specific supplement to the standards and guidelines for clinical genetics laboratories. Genet.Med. (6):444–53. http://dx.doi.org/10.1097/01.GIM.0000172641.57755.3A; PMid:16024978

11. Humphries SE, Ye S, Talmud P, Bara L, Wilhelmsen L, Tiret L. Arterioscler Thromb Vasc Biol. 1995, Jan. 15(1):96–104. European Atherosclerosis Research Study: genotype at the fibrinogen locus (G-455-A beta-gene) is associated with differences in plasma fibrinogen levels in young men and women from different regions in Europe. Evidence for gender-genotype-environment interaction.

12. Copp AJ, Greene ND, Murdoch JN. 2003. The genetic basis of mammalian neurulation. Nat Rev Genet 4:784–792. http://dx.doi.org/10.1038/nrg1181; PMid:13679871

13. May F, Sadiq Ekhlas A, Al-Refai, Amjad Al-Nasser, Mohammad Khassawneh, and Qasem Al-Batayneh. 2011, January/February. Methylenetetrahydrofolate Reductase Polymorphisms C677T and A1298C as Maternal Risk Factors for Down Syndrome in Jordan. Genetic Testing and Molecular Biomarkers 15(1–2):51–57.

14. Yamada K, Chen Z, Rozen R, Matthews RG. 2001, December. «Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase» (//www.ncbi.nlm.nih.gov/pmc/articles/PMC64948). Proc. Natl. Acad. Sci. U.S.A. 98 (26): 14853–8. doi: 10. 1073/pnas.261469998(http://dx.doi.org/10.1073%2Fpnas.261469998) . PMC 64948 (//www. ncbi. nlm. nih. gov/pmc/articles/PMC64948). PMID 11742092(//www.ncbi.nlm.nih.gov/pubmed/11742092).

15. Takayuki Iwaki, Mayra J. Sandoval-Cooper, Melissa Paiva, Takao Kobayashi, Victoria A. Ploplis, and Francis J. Castellino PMC1867160Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse// Am J Pathol. Mar 2002; 160(3): 1021–1034.doi: 10.1016/S0002-9440 (10)64923-1PMCID.