Obstetric history data and some clinical features of pregnancy in the four groups are shown in Table 1. The average age of patients in group 4 was 31.67 ± 4.57 years which was slightly higher than in the other groups. Patients of groups 2 and 4 had a 1.5-fold higher frequency of abnormalities of menstrual function compared to those in group 1. One-third of the women in group 4 suffered temporary sterility.

Cardiovascular disease was common in the patients of all groups. Half the women in group 4 had hypertension or hypotension and varix in their obstetric data. Urogenital infection was present in about one-half of those in groups 1 and 4 (66.2%) and of those in groups 2 and 3 (76.9%), respectively.

Nephropathy as a complication of the current pregnancy was most frequent in women in group 2 (44.9%) (Table 1). Obstetric history of the women in group 4 was more complicated by extragenital pathology and nephropathy than in the women of group 3.

Characteristics of the newborns in four groups are summarized in Table 2. Their average birth weight was 2840.31 ± 809.31 in group 2 and 2664.52 ± 772.67g in group 4. This discrepancy was primarily due to fetus hypotrophy at the term of pregnancy as well as to premature birth. The average birth length of newborns in groups 2 and 4 was 47.92 ± 6.25 and 47.01 ± 4.95 cm, respectively (Table 2). It should be noted that intrauterine growth restriction of fetus confirmed at birth was diagnosed for 39% in group 2 and for 50% of newborns in group 4.

The frequencies of alleles and genotypes of the ACE gene in the four studied groups are shown in Table 3. The frequency of the D allele of the ACE gene in group 1 (51.4%) and that in group 2 (61.3%) did not differ significantly (p >0.05) and was comparable to that in a population from northwest Russia (64.0%) [17]. However, the distribution of ACE genotypes was significantly different in groups 1 and 2 [p <0.01; degree of freedom (df) = 2). The frequency of the D/D genotype was essentially lower (22.2%) in group 1 compared to 46.4% in group 2. The relative risk of PI in the placenta of the D/D genotype from the patients without PM (group 2) was increased 3-fold compared to the patients of group 1 (OR: 3.01, CI: 1.18-7.76). Moreover, the frequency of the I/D genotype of placentae in group 1 was 2-fold more when compared to that in group 2 (58.3 and 29.6%, respectively) (Table 3).

In the anamnesis of women with PM, the frequencies of alleles of the ACE gene were also significantly different in the groups of placental samples. The frequency of the I allele in group 3 (PM+ and PI–) was 2-times less frequent compared to group 4 (PM+ and PI+) (30.4 and 64.6%, respectively, p <0.001) (Table 3). The distribution of the genotypes between groups 3 and 4 was also significantly different (p <0.01; df = 2). The frequency of the I/I genotype in group 3 (8.7%) was decreased 5-times compared to group 4 (45.9%). Thus, the I/I genotype of the ACE gene in placentae increases 7-times the risk of PI development in PM+ women (OR: 7.33, CI: 1.86-28.9).

Further analyses included comparison of all the studied groups. Distribution of ACE gene genotypes (D/D, I/D and I/I) varied significantly in four studied groups (?<0.01; df=6). The frequency of the D/D genotype in group 2 (46.4%) was significantly higher than in group 4 (16.6%) (Table 3). Also, the frequency of the D/D genotype was 2- times lower in group 1 (PM– and PI–) compared to group 3(PM+ and PI–) (22.2 and 47.8%, respectively). It should be stressed that the I/I genotype of the ACE gene dominated in placentae from group 4 (45.9%) compared to all other groups, whereas the I/D genotype prevailed in group 1 (58.3%). Thus, the D/D genotype of the ACE gene in placentae is associated with a 3-fold increased risk of PI development in PM– women, whereas the I/I genotype correlates with a 6-fold risk of development of both pathologies.

 

Parameters	Group 1: PM– and PI–	Group 2: PM– and PI+	Group 3: PM+ and PI–	Group 4: PM+ and PI+
Number of patients	36	54	23	24
Age (years)	27.93±6.17	27.60±7.16	29.17±5.16a	31.67±4.57a
Menstrual cycle abnormalities (%)	48.78±7.80	61.22±6.96	51.30±9.68	71.42±9.85
Temporary sterility (%)	9.75±4.63	10.20±4.32	11.53±4.32	33.3±10.28a
Number of pregnancies	2.04±1.26	2.06±1.60	4.07±2.71	3.76±1.67
Cardiovascular diseases (%)	24.39±6.70	30.61±6.58	38.46±9.54	47.62±10.89
Urogenital infections in current pregnancy (%)	53.65±7.78	66.22±6.96	76.92±8.26a	52.38±10.89
Nephropathy in current pregnancy (%)	24.39±6.70	44.89±7.10a	26.90±8.69	33.30±10.28
Term of the present delivery (weeks)	38.95±1.69	37.74±3.35	38.80±2.06	36.71±3.06

Values are presented as mean ± SEM (standard error of mean).

a p <0.05 (difference between group 1 and others).

Table 2. Phenotypic features of the newborns in the four groups.

Parameters	Group 1: PM– and PI–	Group 2: PM– and PI+	Group 3: PM+ and PI–	Group 4: PM+ and PI+
Male/Female	15/21	30/24	14/9	8/16
Apgar scale (points)	7.78±0.45	7.31±1.11	7.31±1.49	7.15±1.57a
Birth weight (g)	3364.52±515.84	2840.31±809.31a	3332.30±650.95	2664.52±772.67a
Birth length (cm)	50.70±2.38	47.92±6.25a	50.38±3.54	47.01±4.95a
Intrauterine growth restriction of the fetus (%)	–	38.90±6.63	–	50.00±10.21

Values are presented as mean ± SEM.

a p <0.05 (difference between group 1 and others).

Table 3. Frequency distribution of alleles and genotypes of the ACE gene in 4 groups of placentae from parturient women.

Alleles/Genotypes	Group 1: PM– and PI–	Group 2: PM– and PI+	p	Group 3: PM+ and PI–	Group 4: PM+ and PI+	p
Alleles: • D • I	51.4% (37) 48.6% (35)	61.3% (65) 38.7% (41)	0.18	69.6% (32) 30.4% (14)	35.4% (17) 64.6% (31)	0.001
Co-dominant model: • D/D • I/D • I/I	22.2% (8) 58.3% (21) 19.5% (7)	46.4% (25) 29.6% (15) 24.0% (13)	0.01	47.8% (11) 43.5% (10) 8.7% (2)	16.6% (4) 37.5% (9) 45.9% (11)	0.009
Dominant model: • D/D • I/D+I/I	22.2% (8) 77.8% (28)	47.2% (25) 52.8% (28)	0.02	47.8% (11) 52.2% (12)	16.7% (4) 83.3% (20)	0.02
Recessive model: • D/D+I/D • I/I	80.6% (29) 19.4% (7)	75.5% (40) 24.5% (13)	0.57	91.3% (21) 8.7% (2)	54.2% (13) 45.8% (11)	0.004

Number of cases are in parentheses.