Matrix metalloproteinase-7 A-181G and its interaction with matrix metalloproteinase-9 C-1562T polymorphism in preeclamptic patients: association with malondialdehyde level and severe preeclampsia.

PURPOSE: The abnormal activation of matrix metalloproteinases (MMPs) during pregnancy might be involved in the pathogenesis of preeclampsia. The aim of present study was to investigate the possible influence of MMP-7 A-181G and its interaction with MMP-9 C- 1562T polymorphism on the risk of preeclampsia and lipid peroxidation level. METHODS: In a case-control study the MMP-7 A-181G and MMP-9 C-1562T polymorphisms were studied in 168 preeclamptic and 154 healthy pregnant women from Western Iran. The MMP-7 and-9 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of MMP-7 G allele in mild- (37.4 %) and severe-preeclampsia (45.6 %) and controls (40.3 %) were not significantly different. In preeclamptic patients in the presence of MMP-7 AG + GG genotype there was a significantly higher concentration of malondialdehyde (MDA) (10.52 ± 4.18 µM, p = 0.017) compared to that in AA genotype carriers (9 ± 2.89 µM). Also, in the presence of both MMP-7 G and MMP-9 T alleles the MDA concentration (11.6 ± 4.9 µM) was significantly higher compared to the concomitant presence of MMP-7 A and MMP-9 C wild alleles (9.2 ± 3.1 µM, p = 0.02). There was an interaction between two alleles of MMP-7 G and MMP-9 T that significantly increased the risk of severe preeclampsia by 1.4-fold (OR = 1.4, 95 % CI = 1.06-1.85, p = 0.016). CONCLUSIONS: The present study indicates lack of a direct influence of MMP-7 A-181G polymorphism on the risk of preeclampsia. However, this polymorphism through elevation of MDA level as a marker of lipid peroxidation and interaction with MMP-9 C-1562T polymorphism might be associated with the risk of severe preeclampsia.

MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress.

OBJECTIVES: We aimed to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T and endothelial nitric oxide synthase (eNOS) G894T polymorphisms with lipid peroxidation, total antioxidant capacity (TAC) and the risk of preeclampsia in preeclamptic women. DESIGN AND METHODS: We screened a sample of 198 unrelated women with mild and severe forms of preeclampsia and 101 unrelated women with normal pregnancy with the eNOS and MTHFR variants using PCR-RFLP method. Also, the serum malondialdehyde (MDA) and TAC levels were determined using HPLC and commercial kits, respectively. RESULTS: The frequency of combined genotypes of MTHFR CT and TT (CT+TT) and T allele tended to be higher in severe preeclamptic women compared to controls. There was no significant difference for eNOS G894T genotype and allele frequencies between patients and controls. A significantly higher level of triglycerides was observed in the presence of combined genotypes of MTHFR CT and TT and also eNOS GT and TT (GT+TT) in preeclamptic women compared to controls with the same genotype. Also, the presence of MTHFR TT genotype in severe preeclamptic women was significantly associated with the increased serum MDA level compared to CC genotype. In severe preeclamptic women the presence of CT and combined genotypes of CT and TT was significantly associated with the decreased TAC level compared to CC genotype. Also, a higher MDA level was observed in mild preeclamptic women with eNOS TT genotype compared to those with GG genotype but the difference was not significant. CONCLUSION: The present study indicates that MTHFR C677T polymorphism through affecting on TG level, lipid peroxidation and oxidative stress might be involved in the pathogenesis of severe preeclampsia.

Evaluation of sleep problems in preeclamptic, healthy pregnant and non-pregnant women.

OBJECTIVE: Sleep problems are common complaints among pregnant women. This study was designed to compare subjective sleep problems in non-pregnancy condition, healthy and preeclamptic pregnancy as a major complication of pregnancy. We hypothesized that some sleep problems are more prevalent in females with preeclampsia. METHODS: In this cross-sectional study, 102 women with preeclampsia, 106 healthy pregnant women in the third trimester and 103 healthy non-pregnant women were selected through random sampling. Age and parity were matched in the three groups. We used Global sleep assessment questionnaire (GSAQ) to check the subjective sleep problems, and then we performed statistical analysis using Analysis of variance (ANOVA) and Pearson Chi-square tests. RESULTS: Our findings revealed significant differences in initial insomnia (p = 0.034), fragmented sleep (p = 0.022), snoring (p<0.001), non-idiopathic insomnia (p = 0.045) and sadness and anxiety (p = 0.001) between the three groups. Some sleep problems were more common in preeclampctic compared to healthy pregnant women including initial insomnia, fragmented sleep, snoring, sleep apnea and non-idiopathic insomnia. Moreover, the subjects with preeclampsia revealed more fragmented sleep, snoring, sadness and anxiety and lack of getting enough sleep due to other activities compared to non-pregnant women. CONCLUSION: Different kinds of sleep problems can occur in subjects with preeclampsia in comparison with the non-pregnant and healthy pregnant subjects. Sleep problems should be evaluated during pregnancy, particularly in pregnant women with preeclampsia, and suitable treatment should be provided for any specific sleep problem.

Multiple-dose vaginal misoprostol and single-dose misoprostol plus oxytocin for termination of second-trimester pregnancy.

OBJECTIVE: To compare 2 different methods-multiple doses of misoprostol and a combination of misoprostol and oxytocin-for termination of pregnancy in the second trimester. METHODS: Between 2006 and 2008, 120 women undergoing termination of second-trimester pregnancy in 2 hospitals in Kermanshah, Iran, were enrolled in a randomized trial comparing 2 treatments. In each treatment group, an initial vaginal dose of 600 µg of misoprostol was placed in the posterior fornix. After 6 hours, an intravenous infusion of concentrated oxytocin was given to women in group A, and 400 µg of vaginal misoprostol was given every 6 hours to women group B, up to a maximum of 4 doses. The outcomes were compared via χ(2) and independent t tests. RESULTS: Within 30 hours, 96.7% of women in group A and 96.7% of women in group B delivered successfully. The average duration between induction and delivery time was 12.3±6.0 hours in group A and 12.1±6.0 hours in group B (P>0.05). CONCLUSION: The use of misoprostol with oxytocin, and multiple doses of misoprostol gave similar results for termination of pregnancy in the second trimester.

Thrombophilic mutations and susceptibility to preeclampsia in Western Iran.

The aim of the present study was to investigate the frequency and the possible association between thrombophilic mutations of factor V Leiden (FVL) and prothrombin G20210A with preeclampsia among Kurdish population of Western Iran. We studied 198 women with preeclampsia including 128 women with mild and 70 women with severe forms and 101 healthy pregnant women with uncomplicated pregnancy. Among cases there were 23 women with early onset preeclampsia and 175 cases with late-onset preeclampsia. The sample was genotyped by polymerase chain reaction-restriction fragment-length polymorphism using Mnl I and Hind III for FVL and prothrombin G20210A, respectively. The frequency of heterozygous FVL mutation was 7.6% among all preeclamptic women (8.6% in mild and 5.7% in severe preeclamptic women) and 7.9% in controls (P > 0.05). However, the prevalence of heterozygous FVL were 10.5 and 3.9% among severe preeclamptic women with early onset and late-onset preeclampsia, respectively (P > 0.05). The prevalence of prothrombin G20210A were 1.6, 2.9, and 3% among women with mild preeclamsia, severe preeclampsia and controls, respectively (P > 0.05). The level of serum triglycerides (TG) was significantly higher among women with preeclampsia compared to healthy pregnant women that was not associated with the two thrombophilic mutations. Our results indicate that neither FVL nor prothrombin G20210A could be a risk factor for preeclampsia in our population. However, high prevalence of FVL in preeclamptic women with early onset compared to those with late-onset preeclampsia may suggest a role for this mutation in predisposition to early onset preeclampsia that need to be confirmed with larger sample size.

The frequency of factor V Leiden mutation, ACE gene polymorphism, serum ACE activity and response to ACE inhibitor and angiotensin II receptor antagonist drugs in Iranians type II diabetic patients with microalbuminuria.

The aim of present study was to determine if factor V Leiden (FVL) mutation and angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism are associated with diabetic nephropathy (DN) among Kurdish population from Western Iran. This case-control study comprised 144 unrelated adult type 2 diabetic mellitus patients (T2DM) including 72 patients with microalbuminuria and 72 age and sex matched patients without nephropathy. The ACE I/D polymorphism and FVL mutation were detected by polymerase chain reaction (PCR) and PCR-RFLP, respectively. The frequency of FVL G1691A and ACE D allele in T2DM patients with microalbuminuria were 1.6 and 57%, respectively and in normoalbuminuric T2DM patients were 4.9 and 58.3%, respectively (P > 0.05). ACE genotypes affected on serum ACE activity and a better response to ACE inhibitor therapy (captopril) compared to angiotensin II receptor antagonist (losartan) was obtained with significant reduction of ACE activity in diabetic patients without nephropathy carrying DD genotype. However, the beneficial effect of losartan therapy was observed in microalbuminuric patients with II genotype compared to ID and DD genotypes.

Plasma lipids and lipoproteins in children and young adults with major ß-thalassemia from western Iran: influence of genotype.

To determine the plasma lipid and lipoprotein profiles and their possible association with the type of ß-thalassemia mutation we studied 103 major ß-thalassemia patients including 71 children and 32 young adults compared to 102 healthy subjects consisted of 90 children and 12 young healthy adults. The plasma lipid and lipoprotein levels were measured by conventional methods. Considering all of the patients the levels of total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) were significantly lower compared to controls. However, the level of TG was significantly higher in cases than controls. Comparing thalassemic patients homozygous for a ß0 type of mutation with those homozygous for a ß+ type of mutation (IVSI.110 G:A) indicated that the levels of LDL-C, TC were significantly increased and TG concentration tended to be higher in the latter patients. In conclusion, our study indicates that hemolytic stress results in hypocholesterolemia in major ß-thalassemia patients and the presence of more severe genotype in patients is correlated with more reduction in TG, TC, and LDL-C levels.

Factor V G1691A, prothrombin G20210A and methylenetetrahydrofolate reductase polymorphism C677T are not associated with coronary artery disease and type 2 diabetes mellitus in western Iran.

There are controversial results related to the contribution of factor V Leiden G1691A, prothrombin gene G20210A and methylentetrahydrofolate reductase (MTHFR) C677T mutations in the development of coronary artery disease (CAD) and their association with diabetes. To assess the distribution of these thrombophilic mutations in CAD patients with and without type 2 diabetes mellitus (T2DM), we studied 117 CAD patients [65 CAD patients with diabetes (CAD/T2DM) and 52 CAD patients without diabetes (CAD/ND)] and 59 age-matched and sex-matched healthy individuals without CAD from population of western Iran. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism using Mnl I, Hind III and Hinf I for factor V Leiden, prothrombin G20210A and MTHFR C677T, respectively. The prevalence of prothrombin G20210A variant in CAD/T2DM, CAD/ND and control individuals was 3.1, 1.9 and 0%, respectively. Factor V Leiden G1691A was found in 4.6% of patients with CAD/T2DM, 3.8% of patients with CAD/ND and 3.4% of healthy individuals. The prevalence of MTHFR C677T was found to be 49.2, 32.7 and 44.1% in CAD/T2DM, CAD/ND and control group, respectively. Our results indicate that there is no significant difference between the prevalence of thrombophilic mutations of factor V Leiden, prothrombin G20210A variant and MTHFR C677T in CAD patients with or without diabetes compared with controls. Although a higher prevalence of these thrombophilic mutations was observed in CAD patients, especially in those patients with diabetes, it seems that these variants may not be considered as independent risk factors for CAD or diabetes in our sample. These findings are discussed in relation to available literature.

Insulin changes in preeclamptic women during pregnancy.

BACKGROUND: The etiology of preeclampsia remains obscure. To study the role of insulin resistance in preeclampsia, we compared fasting insulin and glucose changes during the second and third trimesters in preeclamptic women with a normal control group. PATIENTS AND METHODS: In a nested case-control study, subjects were selected from a population-based cohort of 674 pregnant women from whom serum was collected for this study between the 20th and 24th week of gestation. For 16 women who developed preeclampsia (cases), 16 women who remained normotensive were selected as controls. Controls were matched with each case for pregestational body mass index, age, gestational age, and parity. Fasting glucose and insulin levels of the second trimester (20th to 24th weeks) of pregnancy were compared based on serological data. The comparisons were also carried out in the third trimester when preeclampsia occurred. RESULTS: Fasting insulin levels increased from 15.3+/-1.3 microlU/mL to 25.3+/-1.4 microlU/mL between the second and third trimesters in the preeclamptic group (P<0.01) and from 10.4+/-0.9 microlU/mL to 16.2+/-1.3 microlU/mL in the control group (P<0.01). There was no significant change in glucose levels during pregnancy in either group. CONCLUSION: Women who develop preeclampsia have higher insulin levels before clinical evidence of disease than women who remain normotensive during pregnancy. The increase in insulin levels in the third trimester was greater in preeclamptic than in non-preeclamptic women.