The role of ABC transporters' gene polymorphism in the etiology of intrahepatic cholestasis of pregnancy.

OBJECTIVES: The etiology of intrahepatic cholestasis of pregnancy (ICP) involves environmental, hormonal and genetic factors. It is thought that ICP may be related to the polymorphic variants of several genes involved in the metabolism and transport of bile acids (BA). The goal of our study was to evaluate the possible role of genetic polymorphic variants of ABC transporters in patients with ICP. MATERIAL AND METHODS: 96 women with ICP (mean age of 30.42 years, mean gestational age of 36.83 gestation weeks) and 211 healthy pregnant women (mean age of 30.68 years, mean gestational age of 39.05 gestation weeks) were enrolled in the study. Genetic analysis was performed using a polymerase chain reaction / restriction fragment length polymorphism (PCR/RFLP) method. The following polymorphisms were analysed: 1331T > C (V444A) ABCB11 and 1954A > G (R652G) ABCB4. RESULTS: Our analysis of frequency of genotypes and alleles of the 1954A > G ABCB4 polymorphism revealed no significant differences between the ICP and control groups. For the 1331T > C polymorphism of the ABCB11 gene the results revealed a higher frequency of 1331CC genotypes in the ICP group (39.58% vs. 29.38%. OR = 1.57, p = 0.05). Also, the frequency of the 1331C allele was higher in the ICP group compared to the control group (64.06% vs. 55.69%, OR = 1.42, p = 0.03). CONCLUSIONS: The overrepresentation of mutated variants of the 1331T > C ABCB11 polymorphism in the ICP group suggests its contribution to the etiology of the intrahepatic cholestasis of pregnancy. Analysis of genotypes' co-existence pointed to the possibility of the mutated variants of polymorphism 1954A > G ABCB4 and 1331T > C ABCB11 having a summation effect on the development of ICP.

Demographic factors determining folic acid supplementation in pregnant and childbearing age women.

OBJECTIVES: Adequate folate intake constitutes a significant problem in the periconceptional period and early pregnancy but can be achieved by folic acid (FA) supplementation. Low intake of folate may cause numerous negative effects on the pregnancy outcome, including recurrent miscarriage, preeclampsia, fetal hypotrophy, premature delivery, premature placental abruption, and intrauterine fetal death. The aim of the study was to evaluate factors determining FA supplementation in the population of Polish women before and during pregnancy. MATERIAL AND METHODS: The study group consisted of 257 women hospitalized postpartum at the Division of Perinatology and Women's Diseases, Poznan University of Medical Sciences, Poland. We evaluated folic acid intake considering selected demographic data. A structured questionnaire was used to evaluate folic acid intake before and during pregnancy of the investigated women. RESULTS: The vast majority of the investigated women (89.1%) took FA during pregnancy. During the pre-pregnancy period, a statistically significantly higher supplementation of folic acid was observed among women with the monthly income level of > 5000 PLN (p = 0.03), and among women who planned their pregnancy as compared to women who did not plan their pregnancy (p < 0.001). During pregnancy, these differences disappeared. A statistically significantly higher number of secundi- and multiparas did not take FA during pregnancy as compared to primiparas (p = 0.008). No correlation between cigarette smoking and FA intake was observed. CONCLUSIONS: Our analysis showed that FA intake increased (by 36.2%) during pregnancy as compared to the pre-pregnancy period, and depended on income, parity, and pregnancy planning.

Importance of polymorphic variants of Tumour Necrosis Factor - α gene in the etiology of Intrauterine Growth Restriction.

OBJECTIVES: Intrauterine growth restriction (IUGR) is one of the main global causes of increased perinatal mortality and fetal and neonatal morbidity. It remains a key challenge for modern perinatal medicine. Negative effects of IUGR are manifested not only in the perinatal period but also at the later stages of life. Proinflammatory cytokines and their polymorphisms are hypothesized to play an important role in IUGR pathomechanisms. The aim of the study was to determine the role of selected polymorphisms (-238G >A, -308G >A and -376G >A) of tumor necrosis factor alpha (TNF-α) in the etiology of intrauterine growth restriction. MATERIAL AND METHODS: The study included 120 patients with IUGR (mean age 30.32, mean gestational age 36.34 gestational weeks) and 135 healthy pregnant women (mean age 31.63, average week of delivery 38.76). The investigated polymorphisms were determined by PCR/RFLP methods. RESULTS: Higher frequency of TNF-α mutated allele -308A was found in a subgroup of women whose pregnancy en-ded < 37 weeks (18.5 vs. 12.2% in control , OR = 1.63, p = 0.09) and in the subgroup of women with a score ≥ 3 UAS (20.6 vs. 12.2% in control , OR = 1.86, p = 0.06). Heterozygous genotype -308GA was associated with at least 3 times greater risk of three or four abnormalities in uterine arteries score (41.2 vs. 20.0 in control, OR = 2.80, p = 0.01). CONCLUSIONS: The obtained results suggest that the -308G >A TNF-α gene variant may play a role in the etiology of IUGR in the Polish population, but further studies on larger groups are needed.