Revealing the contribution of Cytochrome P450 to salt-sensitive hypertension using DNA microarray

Z.M. Kuang, Z.J. Huang, Y. Li, G.P. Yang, M.L. Liu, H. Yuan

Department of Cardiology, the Third Xiangya hospital, Central South University, Changsha, China. yuanhong01@vip.sina.com

 

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• Cardiology

BACKGROUND: Salt sensitivity is an important cause of hypertension which is a major public health problem. This study aimed to investigate the contribution of Cytochrome P450 (CYP) to salt-sensitive hypertension with microarray data and bioinformatics analysis.

METHODS: Gene expression data set GSE4800 was downloaded from Gene Expression Omnibus database, including 6 gene chips from 3 Dahl salt sensitive (DS) rat samples and 3 Lewis (LEW) rat samples. Raw data were preprocessed and normalized, and then differentially expressed genes (DEGs) were identified with Limma package. Interaction network was constructed by employing STRING (Search Tool for the Retrieval of Interacting Genes) tool. GO (Gene Ontology) enrichment analysis was performed using FuncAssociate tool and pathway analysis was carried out by EASE (Expressing Analysis Systematic Explorer). BLAST (Basic Local Alignment Search Tool) was applied to explore the sequence homology among CYP3A genes in rat and human based on multiple alignments.

RESULTS: A total of 1264 DEGs, including 1082 up-regulated genes and 182 down-regulated genes were identified between DS and LEW samples. CYP3A2 and CYP3A9 were selected to construct the protein interaction network, which comprised 1653 pairs of interaction relationship among 100 genes. Functional analysis showed that CYP3A2 and CYP3A9 were most significantly related to oxidation reduction and metabolism of xenobiotics by cytochrome P450. Furthermore, the CYP3A2 and CYP3A9 genes in rats had high homology with genes CYP3A4and CYP3A5 in human beings.

CONCLUSIONS: CYP3A4 and CYP3A5 may contribute to salt-sensitive hypertension in human which may act as biomarkers for this disease.

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