The Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) polymorphisms in the pathogenesis of preeclampsia in Romanian women: association with the severity and outcome of preeclampsia.

OBJECTIVE: To check whether individual or combined mutated genotypes for Ala-9Val (Mn-SOD) and Arg213Gly (EC-SOD) are associated with preeclampsia; to check the influence of the mutated genotypes on the degree of severity and perinatal outcome of preeclampsia. METHODS: We genotyped 97 pregnant women (47 with preeclampsia and 50 normal pregnant women) using PCR-RFLP analysis. RESULTS: The Val/Val (Mn-SOD) genotype (OR 5.99, p = 0.004) but not the Gly/Gly (EC-SOD) genotype (OR 4.23, p = 0.027) was significantly associated with preeclampsia. Higher frequency of both polymorphisms in women with preeclampsia (42.55%) compared to normal pregnant women (8%). Higher frequency of women diagnosed with PIH (27.27%, OR 4.31), mild (50%, OR 11.5) and severe preeclampsia (37.5%, OR 6.9) positive for both polymorphism compared to control women (8%). There was a statistically significant difference in gestational age at delivery according to Mn-SOD (Ala/Ala vs. Val/Val, 39 ± 1.41 weeks vs. 32.77 ± 3.7 weeks) and EC-SOD genotypes (Arg/Arg vs. Gly/Gly, 37.05 ± 3.18 weeks vs. 31.5 ± 3.84 weeks). There also was a statistically significant difference in birth weight according to Mn-SOD (grams, Ala/Ala vs. Val/Val, 3080 ± 481.66 vs. 2376.92 ± 916.88) and EC-SOD genotypes (grams, Arg/Arg vs. Gly/Gly, 2934.09 ± 662.14 vs. 2080 ± 721.19). CONCLUSIONS: Our study demonstrates a relationship between these two mutated genes, the clinical severity and the perinatal outcome of preeclampsia.

Maternal/newborn genotype contribution of the renin-angiotensin system (Met235Thr, Thr174Met, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A- AT2R2, 83A/G-REN) to the risk of pre-eclampsia: a Romanian study.

INTRODUCTION: We evaluated the association of the mutated genotypes Met235Thr-AGT, Thr174Met-AGT, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A-AT2R2, (83)A/G-REN with the risk and outcome of pre-eclampsia; we also investigated whether genes in newborns increase maternal risk of pre-eclampsia. MATERIALS AND METHODS: Thirty-six pairs of pre-eclamptic women and their newborns were genotyped, along with 71 pairs of controls (mothers/newborns) using PCR-RFLP analysis. RESULTS: The Thr235/Thr235 (OR 3.44, p = 0.01), DD (OR 2.66, p = 0.039), CC1166 (OR 5.56, p = 0.04), AA3123 (OR 3.77, p = 0.03) and GG(83) (OR 8.32, p = 0.006) genotypes are significantly associated with pre-eclampsia. Women with pre-eclampsia positive for Met235Thr (34.64 ± 3.92 weeks vs. 38 ± 2 weeks), Thr174Met (32.58 ± 3.92 weeks vs. 36.38 ± 3.25 weeks), I/D (34.47 ± 3.67 weeks vs. 38.33 ± 3.5 weeks) delivered at a significant lower gestational age compared with pre-eclamptic women with a normal genotype. Newborns from women with pre-eclampsia positive for Thr174Met (2190 ± 820.21 g vs. 2702.08 ± 967.23 g), I/D (2399.33 ± 938.38 g vs. 3191.66 ± 684.40 g) had a significant lower birth weight compared with newborns from women with normal pregnancies. When both the mother and the newborn were positive for Met235Thr, I/D, A2350G, A1166C or (83)A/G polymorphisms, the risk for pre-eclampsia was significantly increased at 6.67 (p < 0.01), 5 (p < 0.01), 3.33 (p = 0.006), 2.72 (p = 0.04) and 7.8 (p < 0.01), respectively. CONCLUSIONS: The results of our study confirm that, in pre-eclampsia, both maternal and newborn genetic variations implicated in blood pressure regulation are important.

Correlation between the TSHRc-Asp727Glu polymorphism and plasma thyroid stimulating hormone levels in Romanian preeclamptic women.

AIM: To analyze the influence of thyroid stimulating hormone (TSH) levels and/or the Asp727Glu polymorphism on the severity and perinatal outcome of preeclampsia. METHODS: Forty-nine women with preeclampsia and 58 normal pregnant women were genotyped for the TSHRc-Asp727Glu polymorphism using PCR-RFLP methods. The plasma TSH levels were measured by ELISA method. RESULTS: Fourteen (77.78%) women of 18 pregnant women with abnormal TSH levels had preeclampsia compared to 35 (39.33%) of 89 pregnant women with normal TSH levels who had preeclampsia (OR 5.4, p = 0.003). The mean TSH levels were 2.13 ± 1.44 µU/ml, 2.47 ± 2.03 µU/ml and 4.27 ± 2.75 µU/ml in women with pregnancy induced hypertension (PIH), mild and severe preeclampsia, respectively. OR for PIH and mild preeclampsia was 1.08 (p = 1) and 9.45 (p = 0.06), respectively, in association with the Asp/Asp genotype. All women with severe preeclampsia had the Asp/Asp genotype. The risk for preeclampsia in association with TSH > 4 µU/ml and Asp/Asp genotype is 20.8 (p < 0.01). Preeclamptic women with TSH levels > 4 µU/ml and the Asp/Asp genotype delivered earlier (weeks, 34.92 ± 4.33 vs. 36.6 ± 3.21, p = 0.3) neonates with lower birth weight (grams, 2361.54 ± 1155.81 vs. 3000 ± 1072.38, p = 0.3) than preeclamptic women with TSH levels  < 4 µU/ml and the Asp/Glu genotype. CONCLUSIONS: Higher TSH levels and/or the TSHRc-Asp727Glu polymorphism represent risk factors for preeclampsia and could be correlated with the severity of preeclampsia.

Renin angiotensin system polymorphisms in patients with metabolic syndrome (MetS).

BACKGROUND: The genes associated with hypertension could be genetic risk factors for metabolic syndrome (MetS). AIM: To determine the frequency of M235T and T174M-AGT, I/D-ACE and A1166C-AGTR1 in hypertensive patients with MetS and to evaluate the relationship between these polymorphisms and central obesity and dyslipidemia, respectively. MATERIALS AND METHODS: We performed AGT, AGTR1 and ACE genotyping in 56 hypertensive women (24 with MetS) and 71 normotensive women using PCR-RFLP methods and PCR, respectively. RESULTS: Hypertensive patients carrying the mutated TT235, MM174 and DD genotypes had an 1.53 (p=0.56), 1.78 (p=0.52) and 1.28 (p=0.78)-fold increased risk to develop MetS. Hypertensive carriers of both mutated TT235 and MM174 or TT235 and D/D or TT235 and CC+AC genotypes had an 8.15 (p=0.04), 4.83 (p=0.04) and 10.53 (p=0.05)-fold increased risk to develop MetS. Hypertensive patients with MetS and TT, D/D or CC genotypes had higher body mass index compared to hypertensive patients without MetS (p