Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase.

OBJECTIVE: To investigate the potential perinatal effects of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase C677T polymorphism in preeclamptic women. STUDY DESIGN: One hundred twenty preeclamptic women (N = 120) and 101 healthy pregnant controls (N = 101) were recruited and evaluated for frequency of Leiden and 5,10 methylenetetrahydrofolate reductase (MTHFR) mutations using polymerase chain reaction (PCR). Perinatal outcomes were then recorded and analyzed for all study participants and their neonates. RESULTS: Laboratory analysis yielded 22 (18.33%) heterozygous carriers of Factor V Leiden mutation among preeclamptic women and 3 (2.97%) heterozygous carriers among the healthy controls; differences between the two groups were found to be statistically significant [p < 0.001, the relative risk (RR) = 6.17, 95% confidence interval (95% CI) = 1.90-20.02]. Homozygous MTHFR mutations were found in 8 of 120 (6.67%) preeclamptic women and in 6 of the 101 (5.94%) healthy controls evaluated. Among preeclamptic women, episodes of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome were reported in 7 of 22 (31.81%) of those with Factor V Leiden mutation and in 11 of 98 (11.22%) of those who were negative for the mutation. Group differences were determined to be statistically significant (p < 0.015, RR = 2.83, 95% CI = 1.24-6. 48). Perinatal indicators collected from the two groups included frequency of intrauterine growth retardation, birth weight, and gestational age. No statistically different perinatal outcomes were found between Factor V Leiden positive and negative preeclamptic women. In addition, MTHFR gene polymorphism did not appear to be correlated with the development of preeclampsia. CONCLUSION: Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.

Apolipoprotein E allele distribution in trisomy 13, 18, and 21 conceptuses in a Hungarian population.

Reports documented a higher frequency of apolipoprotein E (apoE) allele epsilon 4 among mothers of children diagnosed with Down syndrome. We studied the prevalence of apoE alleles among 56 conceptuses with trisomy 13, trisomy 18, or trisomy 21. The presence of the 3 most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism, and trisomy status was detected by fluorescent polymerase chain reaction followed by DNA fragment analysis and by conventional cytologic methods. We found no significant difference in the distribution of apoE alleles in the group of trisomy 21 fetuses compared with samples from healthy blood donors. The odds of having trisomy 18 for the apoE epsilon 4 group was 3-fold as high as for apoE epsilon 3 allele compared with the healthy control group. Furthermore, a statistically significant association was found for those with trisomy 18 and apoE epsilon 4, while for those with trisomy 13 and apoE epsilon 4, the test showed no significant association. The observed apoE allele epsilon 3 frequencies among patients with Down syndrome and healthy control subjects may help explain and support previous work that did not find high rates of atherosclerosis among these persons. The role of apoE alleles in the development of trisomies needs further study.

Distribution of apolipoprotein(a) isoforms in normotensive and severe preeclamptic women.

OBJECTIVE: Preeclampsia is a pregnancy-related disorder constituting one of the primary causes of worldwide maternal and fetal mortality, but despite intensive research its pathogenesis remains unclear. Lipids have been implicated in the development of preeclampsia, although this possible association remains controversial and not yet fully investigated. This study set out to examine the potential association between lipoprotein(a) and the development of severe preeclampsia. The focus of this study was to investigate the potential utility of apolipoprotein(a) isoforms as possible diagnostic markers for identifying women at risk for developing preeclampsia. METHODS: Study participants included a control group of nonpregnant female volunteers (n = 59), a group of healthy pregnant (normotensive) female volunteers (n = 51), and a group of severe preeclamptic female volunteers (n = 59). Serum lipoprotein(a) concentrations were measured using double-antibody ELISA methods and were found to be 17.0+/-23.6 mg/dl among nonpregnant controls (n = 51), 15.9+/-15.8 mg/dl among healthy pregnant normotensives (n = 51), and 16.2+/-16.7 mg/dl in the preeclamptic group (n = 59). In addition, apolipoprotein (a) isoforms were identified using high-resolution SDS-agarose electrophoresis followed by immunoblotting. RESULTS: We detected no significant differences between the groups studied in the distribution of isoforms (Chi-square = 1.21, df = 4, P = 0.89); however, in a 1-week interval we detected a 42.2% rise in Lp(a) levels as well as a 67.1% rise in C-reactive protein concentrations among 10 volunteers in the preeclamptic group (median = 9.6; P < 0.05). CONCLUSIONS: Although the exact mechanism of pathogenesis continues to elude investigators, our results suggest that lipoprotein(a) may act as an acute-phase reactant during preeclampsia. Although our results are preliminary, they are consistent with growing evidence implicating lipids as among those factors involved in the etiology of preeclampsia. Changes in apolipoprotein(a) may be among those important biochemical markers that are found to be useful in the early identification of high-risk women and warrant further study.

Apolipoprotein E gene polymorphism frequencies in a sample of healthy Hungarians.

Apolipoprotein E (apo E) has been found to play an important role in lipid metabolism and has been associated with cardiovascular and neurodegenerative conditions. Hungarians have some of the highest rates of cardiovascular morbidity and mortality in the world. This study examines the distribution of apo E alleles and genotypes in a population of healthy ethnic Hungarian blood donors (n = 302). Male (n = 152) and female (n = 150) subjects ranging from 18 to 62 years of age (mean 37.0) were involved. To determine the frequency of apo E alleles, polymerase chain reaction followed by restriction length polymorphism was applied. The analyses of data showed that apo E allele epsilon3 had the greatest frequency in this group (0.807), followed by apo epsilon2 (0.104) and apo epsilon4 (0.087). The highest genotype frequency was found to be epsilon3/3 at 65.2% (n = 197) followed by genotype epsilon3/4 at 15.9% (n = 48), genotype epsilon2/3 at 15.2% (n = 46), genotype epsilon2/2 at 2.3% (n = 7), genotype epsilon2/4 at 1.0% (n = 3) and genotype epsilon4/4 at 0.4% (n = 1). The apo E frequencies found in this study appear to differ from an earlier study of blood donors, where the results are based on apo E phenotyping.