Abstract
Human sex differences in the gene expression of drug metabolizing enzymes and transporters (DMETs) introduce differences in drug absorption, distribution, metabolism and excretion, possibly affecting drug efficacy and adverse reactions. However, existing studies aimed at identifying dimorphic expression differences of DMET genes are limited by sample size and the number of genes profiled. Focusing on a list of 374 DMET genes, we analyzed a previously published gene expression data set consisting of human male (n=234) and female (n=193) liver samples, and identified 77 genes showing differential expression due to sex. To delineate the biological functionalities and regulatory mechanisms for the differentially expressed DMET genes, we conducted a co-expression network analysis. Moreover, clinical implications of sex differences in the expression of human hepatic DMETs are discussed. This study may contribute to the realization of personalized medicine by better understanding the inter-individual differences between males and females in drug/xenobiotic responses and human disease susceptibilities.
Highlights
Sex differences in disease susceptibility, drug efficacy, and drug safety have been observed widely in epidemiological studies as well as in clinical reports [1]
To explore sex differences in the expression of human hepatic Drug Metabolizing Enzyme and Transport (DMET) genes, we focused on analysis of 374 DMET genes profiled on the microarray
A major molecular factor involved in sex-related differences of drug responses and disease development is related to drug-metabolizing enzymes and drug transporters, and likely related to differential expression of DMET genes
Summary
Sex differences in disease susceptibility, drug efficacy, and drug safety have been observed widely in epidemiological studies as well as in clinical reports [1]. Sex differences in the expression of DMETs are thought to be one of the most important determinants accounting for individual differences in clinical pharmacology, pharmacokinetics, and pharmacodynamics [2]. It was found that some drugs were metabolized by certain isoforms of cytochrome P450 with higher rates in male than in female rats (reviewed in [4]). During the last several decades, sex differences in drug responses have been extensively investigated using multiple approaches, such as clinical pharmacology, pharmacogenetics, pharmacokinetics, and pharmacodynamics. This effort attempts to provide information to allow a better understanding of the biological basis of sex differences in order to improve public health
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