Genetic variants of endothelial nitric synthase in gestational hypertension and preeclampsia

Abstract

Aim of the study: To evaluate the correlation of 894G>T (Glu298Asp) and -786T>C polymorphisms of NOS3 gene with the development of preeclampsia (PE) and gestational hypertension (GH). Material and methods: 110 hypertensive pregnant women (mean age 29.46±4.54 years, mean gestational age 36.88±3.50 gw., mean systolic blood pressure 167.82±16.87 mmHg, mean diastolic blood pressure 104.32±11.62 mmHg) were enrolled into the study group. The whole study group was further subdivided into two subgroups: women with gestational hypertension (GH, n=69) and with preeclampsia (PE, n=41). Gestational hypertension and preeclampsia were diagnosed according to the ACOG standards. All patients with multiple pregnancy, diabetes, vascular changes and thrombotic complications were excluded from the study. The control group consisted of 150 healthy pregnant women (mean age 28.29±4.40 years, mean gestational age 39.06±1.28 gw., mean systolic blood pressure112.07±10.75 mmHg, mean diastolic blood pressure 70.62±9.13 mm Hg). The frequency of investigated genotypes of NOS3 gene polymorphisms was examined by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP) method. Results: As far as the 894G>T polymorphism was concerned, a higher frequency of 894TT genotype in the control group in comparison to the whole study group was observed (8.7 vs. 5.4%; WR=0.61, p=ns). A similar observation was made about the 894T allele (25.4 vs. 30.0%, WR=0.79, p=ns). The frequency of the 894T allele was also higher in controls in comparison to the PE group (30% vs. 26.8%, p=ns) and GH group (30% vs. 24.6%, p=ns). Analyzing the -786T>C polymorphism no statistically significant differences between the whole study and the control groups was found. The frequency of the mutated -786CC genotype was similar in the entire study group and controls (13.6 vs. 15.3%, p=ns). The frequency of the mutated -786C allele was also similar in both analyzed groups (37.3 vs. 38.0%, p=ns). A statistically significant difference in the frequency of coexistence of mutated homozygotic genotypes 894TT/-786CC between the investigated groups (0.9% in the whole study group vs. 6.7% in the control group, p=0.019) was observed. Coexistence of 894GT/-786TC genotypes was noted more frequently in the control group (19,1% in the whole study group vs. 24.7% in the control group, p=ns). The frequency of other combinations of investigated genotypes coexistence did not significantly differ between the control group, the entire study group, and the PE and GH groups. In the PE group, a higher systolic blood pressure was noted in patients with -786CC genotype (205.0±21.2 mmHg) in comparison to patients with -786TT (177.0±17.8 mmHg) or -786TC (173.4±13.5 mmHg) genotypes (p=ns). Conclusions: The presence of the 894TT genotype of the 894G>T (Glu298Asp) polymorphism may play a protective role in the development of preeclampsia. The presence of the -786CC genotype of the -786T>C polymorphism may correlate with the increase of the systolic blood pressure in pregnant women with preeclampsia.