Ventskivska I., Proshchenko O.

National O.O. Bogomolets Medical University

Serpin 1 gene polymorphism role the genesis of miscarriage

Miscarriage is considered to me be one of the greatest problem of modern obstetrics. Almost 10-15% of pregnancies are registered to be interrupted spontaneously before 22 gestational weeks. It is described, that majority of early pregnancy losses are happening in the I trimester, and 38% of them in the first 7-8 weeks. During last years a group of publications devoted to the association between thrombophilia as hereditary as acquired and miscarriage are available. According to some authors, the proportion of thrombophilia as a cause of fetal loss syndrome is 40-75%.

We have 256 examined women, had cases of miscarriages and 84 of these 256 (32,8%) were confirmed to have genetic mutations. These 84 had made a main group of trial, this group was divided in to subgroups – I one - 39 patients with 1 miscarriage and II subgroup - 45 patients with 2 or more miscarriages in their history. 37 patients with physiological pregnancy had made a control group. All women were comprehensive survey, which included: clinical research methods, laboratory, determine hormonal, infectious screening, molecular genetic testing mutations serpin 1 675 5G / 4G. We conducted amplification of DNA in vitro, using the method of polymerase chain reaction (PCR).

The results of molecular genetic testing gene polymorphism of serpin 1 (PAI-1) -675 5G/4G surveyed women with different number of abortions compared with controls is presented in Table 1. The analysis of the frequency of mutations PAI-1 675 5G / 4G in the main group has showed a statistically significant decrease in the proportion of normal genotype 5G / 5G women with 1, as well with 2 or more miscarriages in history (51.3% and 57 and 8%, respectively) compared with the control group (75.7%, p <0.05). At the same time the part of women heterozygous mutations carriers of group (28.2%) was slightly higher compared with group II (22.2%) and 1.5 times greater than in the control group (18.9%). Homozygous genotype (20.5% and 20.0% respectively) has been confirmed significantly more frequently than the control group (5.4%) and did not differ within the main group of polymorphic allele 4G par with the highest frequency of diagnosed group I (34, 6%), which is almost double compared with the control group (14.9%)).

Table. 1

Serpin 1 (PAI-1) - 675 5G/4G	The control group, n = 37		Group I n = 39			Group II n = 45
	abs. n.	%	abs. n.		%	abs. n.	%
Genotypes
5G\5G	28	75,7%	20	51,3%*		26		57,8%*
5G\4G	7	18,9%	11	28,2%*		10		22,2%
4G\4G	2	5,4%	8	20,5%*		9		20,0%*
Alleles
5G	63	85,1%	51	65,4%*		62		68,9%*
4G	11	14,9%	27	34,6%*		28		31,1%*

Histological examination revealed changes characterized nuclei pycnosis, cytoplasm coagulation necrosis and reactive cell proliferation. Between the affected cells numerous clots were found. In some cases, there was a slight inflammatory changes with no signs of degradation or infiltration. Such signs as reactive proliferation of blood vessels and blood clots recanalization were dominating with diffuse deposits of hemosiderin and eosinophilic globules.

Describing the group of women with gene polymorphism Serpin 1 (PAI-1) - 675 5G/4G, it should be noted that often encountered difficulties I trimester, which consisted in the formation of retrochorial hematomas in 4 women of 7 in group I (57.1%) and in 5 of 9 group II (55.6%). According to information received, retrohorial/retroamniotyc hematomas occurred among carriers polymorphism Serpin 1-1 675 5G/4G (4G/4G and 5G/4G) with one and with two or more miscarriages almost 2 times more likely (57.1% and 55.6%) than the control group (9.7%). It should be noted also, that retrohorial/retroamniotyc hematomas mainly happened in women with homozygous mutation genotype.

These results confirm the role of gene polymorphisms of PAI-1 675 5G/4G genesis in genesis of pregnancy loss. Odds ratio possible further losses in reproductive mutations Serpin 1 (PAI-1) - 675 5G/4G was 2.57, 95% confidence interval (CI) within 1.11 - 6.38. Homozygous polymorphism of PAI gene mutation is prognostic unfavorable, risk of miscarriage is almost three times higher than in women with genotype 5G/4G (odds ratio was 1.83, 95% confidence interval (CI) within 1.21 - 5.13 and 5.17, 95% confidence interval (CI) within 1.35 - 34.19).

So testing of polymorphism in women with even one miscarriage in history is strongly recommended. In further studies scheme preconception preparation for the next pregnancy to avoid further loss of reproductive and obstetric complications will be optimized.

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