Comprehensive Screening of Gene Function and Networks by DNA Microarray Analysis in Japanese Patients with Idiopathic Portal Hypertension.

Kohei Kotani,Hiroyasu Morikawa,Joji Kawabe,Susumu Shiomi,Makoto Hashizume,Tomohiko Akahoshi

doi:10.1155/2015/349215

Kohei Kotani, Hiroyasu Morikawa + Show 4 more

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https://doi.org/10.1155/2015/349215

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Abstract

The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-β, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism.

Highlights

Idiopathic portal hypertension (IPH) is characterized by portal hypertension due to obstruction or stenosis of the intrahepatic peripheral portal branches [1, 2]
These blood samples had been stored without identifying information at the Sample Storage Center of Kyushu University installed by the Portal Hemodynamics Abnormalities Study Group within the framework of the Intractable Hepatobiliary Disease Program of the Ministry of Health, Labour and Welfare, Japan
The results of the current study showed that the expression levels of CYP4F3 and glutathione peroxidase 3 (GPX3), which are known to be involved in degradation of leukotriene B4 (LTB4) and the LTB4 precursor 5-HPETE, were increased

Summary

Introduction

Idiopathic portal hypertension (IPH) is characterized by portal hypertension due to obstruction or stenosis of the intrahepatic peripheral portal branches [1, 2]. Patients with IPH present with splenomegaly, anemia, and portal hypertension and are free of obstruction of the extrahepatic portal vein or hepatic vein, hematological disease, parasitic disease, granulomatous liver disease, or congenital hepatic fibrosis. IPH resembles a disease called noncirrhotic portal fibrosis in India or hepatoportal sclerosis/noncirrhotic portal hypertension in Western countries [5, 6]. Researchers have suggested that IPH may be attributed to intrahepatic peripheral portal vein thrombosis, splenic factors, abnormal autoimmunity, and related factors [7,8,9,10,11]

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