Correlation between mutation of MDR3 gene exon 6 and parenteral nutrition-associated cholestasis of preterm infants

Xiu Fang Yang,Bing Yi,Guo Sheng Liu

doi:10.3892/etm.2014.1980

Abstract

The aim of this study was to investigate the association between the mutation of multidrug resistance 3 (MDR3) exon 6 and parenteral nutrition-associated cholestasis (PNAC) in preterm infants. A total of 41 preterm infants with PNAC formed the experimental group, and 56 preterm infants receiving total parenteral nutrition (TPN) for >14 days but without cholestasis formed the control group. Genomic DNA was extracted from peripheral venous blood leukocytes. Polymerase chain reaction was used to amplify exon 6 of the MDR3 gene. The target band of MDR3 gene exon 6 was identified in all blood samples from all cases. We identified five cases with C. 504 C>T heterozygous mutations of exon 6 of the MDR3 gene and 14 cases with C. 504 C>T homozygous mutations in the experimental group. In the control group, we identified seven cases with the C. 504 C>T homozygous mutation and six cases with the C. 504 C>T heterozygous mutation. The distribution of the T/C allele frequency of C. 504 in exon 6 of the MDR3 gene between the experimental group and control group was statistically significant (P<0.05). Further analysis revealed the odds ratio of the T/C allele frequency of the C. 504 mutation in exon 6 of the MDR3 gene between the experimental group and control group to be 0.316. Point mutation C. 485 T>A was detected in one case in the experimental group. The C. 504 C>T and C. 485 T>A MDR3 mutations in exon 6 are possibly responsible for the development of PNAC in infants. C. 504 C>T may not be the only risk factor of neonatal PNAC. In order to further confirm the association between exon 6 of the MDR3 gene and PNAC, a large-sample multicenter study should be carried out.

Highlights

Premature infants with gastrointestinal intolerance require total parenteral nutrition (TPN) to enable metabolic growth
The clinical data comparison between the experimental group and control group revealed that the differences in gender, hypoxia, sepsis and hemolytic disease between the two groups were not statistically significant (P>0.05 for all), and that the differences in gestational age and intravenous nutrition time were statistically significant between the two groups (P
The electrophoresis results revealed a clear band of multidrug resistance 3 (MDR3) gene exon 6 amplified fragments

Summary

Introduction

Premature infants with gastrointestinal intolerance require total parenteral nutrition (TPN) to enable metabolic growth. PNAC is defined, based on previously established definitions, as a direct bilirubin level of >2.0 mg/dl following a prolonged course of TPN (>2 weeks) and when other causes, including surgical and metabolic diseases, have been ruled out. Previous studies have suggested that PNAC occurs in premature infants due to premature liver, imperfect bile acid metabolism function and liver uptake ability, disorder of bilirubin enterohepatic circulation, immature gastrointestinal mucosal barrier function and immune system development, lack of fasting gastrointestinal nutrition stimulation, infection, TPN solution imbalance and parenteral nutrition toxic ingredients [3,4,5]. If is not prevented as early as possible, PNAC may develop into cholestasis, liver fibrosis, other irreversible liver damage, liver failure and even mortality. It is necessary to explore the pathogenesis of PNAC

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