Frequency of G2677T/A and C3435T polymorphisms of MDR1 gene in preeclamptic women

Frequency of G2677T/A and C3435T

polymorphisms of MDR1 gene in preeclamptic women

Częstość występowania polimorfizmów G2677T/A oraz C3435T genu MDR1 u kobiet ze stanem przedrzucawkowym

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1 Laboratory of Experimental Pharmacogenetics, Department of Clinical Pharmacy and Biopharmacy, University of Medical Sciences, Poznan, Poland

2 Department of Quality Control of Medicinal Products and Dietary Supplements, Institute of Natural Fibres and Medicinal Plants, Poznan, Poland

3 Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan

4 Laboratory of Molecular Biology in 3Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland

Abstract

Objective: Preeclampsia (PE) belongs to main causes of mortality rates of mothers, fetuses and new born children.

Polymorphism of MDR1 gene is connected with reduction of P-glycoprotein expression in placenta and increased fetal exposure to xenobiotics. The aim of the study was to determine the frequency of C3435T and G2677T/A polymorphisms of MDR1 gene in pregnant women with preeclampsia.

Materials and methods: The study consisted of 180 Polish women including 60 women with PE and 120 healthy pregnant women. Determination of C3435T and G2677T/A polymorphisms of MDR1 gene was performed using PCR-RFLP method.

Results: No significant association between genotypes of the examined polymorphisms and the clinical parameters of pregnant women with PE was observed. However the interesting tendency to higher prevalence of mutated 2677A allele of G2677T/A MDR1 polymorphism in PE group has been shown (2,50 vs. 0,83% in controls, OR=3,05, ns).

Conclusions: The results of this study suggest no significant effect of examined C3435T and G2677T/A MDR1 polymorphisms in PE pathogenesis. However given the noteworthy results related to mutated 2677A allele of G2677T/A MDR1 polymorphism in preeclamptic women further studies seem to be needed. Nevertheless, the frequency of investigated polymorphisms was consistent with the distribution in other Caucasian populations.

Key words: preeclampsia / P-glycoprotein / MDR1 gene / genetic polymorphism /

Otrzymano: 08.02.2013

Zaakceptowano do druku: 30.07.2013 Corresponding author:

Anna Bogacz

Laboratory of Experimental Pharmacogenetics Department of Clinical Pharmacy and Biopharmacy Poznan University of Medical Sciences, Poznan, Poland 14 Św. Marii Magdaleny Street, 60-861 Poznań e-mail: aniabogacz23@o2.pl

Introduction

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Aim of study

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Materials and Methods

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Cel pracy: Stan przedrzucawkowy (PE – preeclampsia) należy do głównych przyczyn śmiertelności matek, płodów i noworodków na świecie. Polimorfizm genu oporności wielolekowej (MDR1 – multidrug resistance gene) jest związana ze zmniejszeniem ekspresji P-glikoproteiny w łożysku i w efekcie zwiększeniem narażenia płodu na działanie ksenobiotyków. Celem badania było określenie częstości występowania polimorfizmów C3435T oraz G2677T/A genu MDR1 u kobiet ciężarnych ze stanem przedrzucawkowym.

Materiały i  metody: Analizie została poddana grupa 180 kobiet populacji polskiej, wśród nich wyróżniono 60 kobiet z PE oraz 120 zdrowych kobiet ciężarnych. Oznaczanie polimorfizmów C3435T i G2677T/A genu MDR1 przeprowadzono za pomocą techniki PCR-RFLP.

Wyniki: Nie wykazano istotnej statystycznie zależności między genotypami analizowanych polimorfizmów a  parametrami klinicznymi i  biochemicznymi ciężarnych z  PE. W  badaniu zaobserwowano jednak interesującą tendencję do większej częstości występowania zmutowanego allela 2677A polimorfizmu G2677T/A  MDR1 w grupie z PE (2,50 vs. 0,83% w grupie kontrolnej, OR=3,05, ns).

Wnioski: Wyniki badania sugerują brak znaczącego wpływu badanych polimorfizmów C3435T i G2677T/A genu MDR1 na patogenezę stanu przedrzucawkowego. Jednak z uwagi na interesujące wyniki dotyczące zmutowanego allela 2677A polimorfizmu G2677T/A  MDR1 u  kobiet z  PE istnieje potrzeba przeprowadzenia dalszych badań.

Obserwowana częstość analizowanych polimorfizmów była zgodna z rozkładem w innych populacjach rasy kaukaskiej.

Słowa kluczowe: stan przedrzucawkowy / glikoproteina P / gen MDR1 /

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Table I. Frequency of genotypes of C3435T and G2677T/A MDR1 polymorphisms in PE and control groups.

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Table II. Comparison of genotypes of C3435T MDR1 polymorphism in PE and control groups with the clinical and biochemical parameters.

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Table III. Comparison of genotypes of G2677T/A MDR1 polymorphism in PE and control groups with the clinical and biochemical parameters.

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Conclusions

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Acknowledgements

This article was supported by Polish Ministry of Science and Higher Education, Grant No N N405 676140.

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