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The role of ABC transporters’ gene polymorphism in the etiology of intrahepatic cholestasis of pregnancy
Affiliations- Department of Gynecology and Obstetrics with Gynecological Oncology Subdivision, Regional Hospital in Zielona Góra, Poland
- Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Laboratory of Molecular Biology, Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland
- Department of Pharmacology and Phytochemistry, Institute of Natural Fibers and Medicinal Plants, Poznan, Poland
- Department of Pharmaceutical Botany and Plant Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
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Abstract
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.
Abstract
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.
Keywords
intrahepatic cholestasis of pregnancy, ICP, bile acid, ABC transporter, polymorphism
About this articleTitle
The role of ABC transporters’ gene polymorphism in the etiology of intrahepatic cholestasis of pregnancy
Journal
Issue
Article type
Research paper
Pages
393-397
Published online
2018-07-31
Page views
1802
Article views/downloads
1518
DOI
Pubmed
Bibliographic record
Ginekol Pol 2018;89(7):393-397.
Keywords
intrahepatic cholestasis of pregnancy
ICP
bile acid
ABC transporter
polymorphism
Authors
Krzysztof Piątek
Grażyna Kurzawińska
Justyna Magiełda
Krzysztof Drews
Magdalena Barlik
Zbyszko Malewski
Marcin Ożarowski
Małgorzata Maciejewska
Agnieszka Seremak-Mrozikiewicz
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