Because of obvious clinical variations of our PE pa­tients they were subdivided into two main groups (pure and combined PE) with several clinical subgroups within each, as indicated in Table 1.

Polymorphism of the PLAT Gene. Endothelial dam­age is usually accompanied by retardation of fibrinolysis, determined by imbalance between tissue type plasminogen activator (t-PA) and by its main inhibitor (PAI-1). Protein products of these genes (PLAT and PAI-1, respectively) are valuable markers of endothelial dysfunction. There are few data concerning the association of the PLAT gene polymorphism (deletion/insertion of Alu-repeats in intron 8) with risk of myocardial infarction and with other car­diovascular diseases. Marked elevation of t-PA level cor­relates with an increase of PLAT gene I-allele frequency, and is considered as a risk factor for myocardium infarc­tion [2,3]. Thus far, nothing is known about the possible association of PLAT polymorphism with PE.

Frequencies of the PLAT genotypes in pure (p) and combined (c) PE patients are presented in Table 1. The frequency of I/I homozygotes in pPE patients does not differ from that in the control group, while in the group of cPE patients the frequency of these genotype is 1.5-2 times more than in the control group.

In severe cPE with arterial hypertension (nephropathia II-III and real PE) the genotype I/I frequency (twice ex­ceeded) that in cPE as a whole and was three times more than that of the control. However the small number of patients in this group does not reveal a statistical signifi­cance of these differences (c² = 2.95; p<0.5). The highest frequency of I/I genotype (33.3%) was found in cPE pa­tients with gestational diabetes  (c² = 4.22; p<0.25).

Thus, deletion/insertion Alu polymorphism of the PLAT gene may contribute to the pathogenesis of cPE. It may also promote the advancement of background dis­eases associated with endothelial dysfunction and throm­bophilia. Most likely, the I/I genotype predisposes to cPE with arterial hypertension and gestational diabetes as its background. The absence of D/D homozygotes in the pa­tients with severe forms of pPE and with diabetes mellitus type 1 or 2 background remains the subject for further studies.

Polymorphism of the PAI-1 Gene. Gene PAI-1 has an insertion/deletion G-base polymorphism (4G/5G) in its promotor region [4]. It has been shown that inherited fibrinolysis impairment in pregnant women with some common obstetrical complications (heavy PE, abruptio placentae, fetal growth retardation and stillbirth) was asso­ciated with polymorphism of the gene PAI-1 in such a way that the 4G/4G genotype was linked to an increased risk of PE and thrombosis [5].

Genotype frequencies of the 4G/5G PAI-1 polymor­phism in pPE and cPE are given in Table 1. The frequen­cies of the 4G/4G genotype in all groups of pPE appeared significantly above control level at the expense of substan­tial reduction in the number of relevant heterozygote (4G/5G) and homozygote (5G/5G) specimens. These re­sults demonstrate that the 4G/4G genotype is associated with pPE.

Its frequency in cPE is higher than the control values, but somewhat lower than in PE patients as a whole. The 4G/4G genotype was found exclusively in severe cPE patients with kidney disease. Only in some cPE subgroups with mild and severe arterial hypertension did frequencies of 4G homozygotes reach a statistically significant level (c² = 3.6 and even 4.77). Some trends in reduction of 4G homozygotes were detected in the cPE patients who had the added complication of diabetes mellitus (c² = 2.55).

Thus, it seems plausible that the PAI-1 polymorphism is involved in the development of PE. The association of the 4G/4G genotype is especially evident for pPE and for cPE, complicated by arterial hypertension and by concom­itant kidney disease.

Polymorphism of the ACE Gene. The angiotensin-converting enzyme (ACE) is a major component of the renin-angiotensin system, responsible for the conversion of angiotensin I to angiotensin II and for bradykinin inacti­vation. Its participation in augmentation of endothelial dysfunction and vasoconstriction is unequivocal. Data concerning the association of its polymorphism [deletion (D)/insertion (I)] of ALU-repeats in intron 16 with PE are scanty and inconsistent. According to one observation, the I/I genotype should be considered as a marker of reduced PE risk, while homozygosity for Alu deletion (D/D geno­type) is the marker of its increased PE risk [6]. These findings are not supported by the other studies [7].

Data on the frequencies of the ACE genotypes are presented in Table 2. There is a marked increase in both types of homozygotes (I/I and D/D) in the pPE group, especially in the patients with pPE corresponding to neph­ropathia I and II (c² = 9.1). In cPE the increase in the num­ber of D/D homozygotes was also quite obvious, especially among patients with mild cPE augmented by heavy AH (c² = 3.36). On the other hand, in severe pPE and in the subgroup of severe cPE with mild AH, the frequency of the D/D genotype was more than twice below that of the control value (c² = 10.4). The distribution of the ACE genotypes was within normal ranges in cPE patients with accompanying kidney disease.

Thus, the greatest difference from the control group in the frequencies of ACE polymorphism is seen in pPE group corresponding to nephropathia I and II. The associa­tion of this polymorphism with cPE is less evident. At present, it can mainly be attributed to cPE complicated by AH. The insufficient number of patients in separate sub­groups does not permit a final conclusion on the associa­tion of the D/D ACE gene genotype with various forms of cPE.

Polymorphism of the eNOS Gene. Endothelial nitric oxide synthetase (eNOS) participates in NO synthesis in the endothelium and, hence, in regulation of a vascular tone, circulation and blood arterial pressure [8]. The 4a/4b polymorphism in intron 4 of the eNOS gene (Table 1) was found to be associated with increased risk of PE [9]. Pre-eclampsia patients with even only one 4a allele demon­strated elevated arterial blood pressure. Earlier manifesta­tion and heavier progression of PE was found in 4a/4a homozygotes [10]. The detrimental effects of this allele were especially pronounced in early pregnancy and ap­peared to decrease with gestational age [11].

Distribution of eNOS genotypes in our PE patients and in the control group is shown in Table 2. Not a single 4a/4a genotype was identified in pPE patients, and it was rather rare in both control and cPE groups. The genotype 4a/4b was detected in patients with mild pPE, whereas all pregnant women with severe pPE had genotype 4b/4b (c² = 8.2). The association of a 4a/4b polymorphism with mild forms of cPE in combination with AH was observed. The increase of 4a homozygotes and decrease in 4b allele frequencies were statistically significant in patients in this category (c² = 4.87). The 4a/4a genotype was also encoun­tered in cPE patients with diabetes mellitus type 1. No other subgroups of cPE patients carried this genotype. Thus, the 4b/4b genotype of the eNOS gene correlates with heavy pPE, while genotype 4a/4a dominates in some forms of cPE.

Polymorphism of the TNF-a Gene. TNF-a is one of the most aggressive inflammatory cytokines. Its increased activity is known to stimulate generation of free radicals, induces apoptosis and accompanies endothelial dysfunc­tion [10]. The data on association of the TNF-a gene poly­morphism with endothelial dysfunction are conflicting [12,13].

As may be inferred from Table 2, only two genotypes (–238)G/G and (–238)A/G, were found in both PE and in the control groups. In the subgroup with heavy pPE only G/G homozygotes were noted. In cPE complicated with arterial hypertension, a marked increase of heterozygote frequency was found. It was especially significant in cPE patients with mild arterial hypertension (c² = 8.53) and with kidney disorders (c² = 9.97).