Gene expression profiles as biomarker in human biomonitoring

Subtitle:Study of time-bound variation in gene expression and relationships with exposure and effects of environmental pollution

Within the framework of a preventive environmental and health policy, there is a strong need for the development of new biomarkers of exposure and/or effect of environmental contaminants, which already at an early stage give an indication of possible health effects. Measuring gene expression in peripheral blood using microarray is an attractive concept. The underlying hypothesis is that circulating blood reflects the physiological response of an organism and that these blood cells, and more specifically lymphocytes, adapt their transcriptome (gene expression profile) according to the health status of the host. Monitoring gene expression profiles is therefore considered a promising approach for the identification of sensitive biomarkers within a human biomonitoring programme. This study aims to contribute to the identification of sensitive markers of adverse effects that already give an indication of health effects at an early stage. In a first work package, a literature study was made of the possibilities and difficulties in the use of gene expression as biomarker in human environmental bio-monitoring, and the possible advantages compared to traditional biomarkers. An important requirement for using gene expression in biomonitoring is that normal transcriptional variability is documented. It is important to characterize the variation at the population level, but also time-bound variation at the individual level. Only if such background values are known, can gene expression profiles obtained after exposure to pollutants be used to determine whether there is a significant increase or decrease in gene expression. In this study, the stability of gene expression in blood in function of time was investigated on the basis of data from a study population of healthy adults. Short and long term variability in gene expression was described and analysed. Emphasis was placed on seasonal and gender influence. In a third research section, the impact of pollutant exposure on gene expression was investigated. The policy usefulness of gene expression profiles in the context of a human biomonitoring monitoring network is discussed.
The study indicated that in an environmental health context the measurement of gene expression is promising but not yet as developed as for clinical applications. The technology appears to be robust but there is a continuous evolution in the field of data processing and interpretation. The short-term and seasonal variability of individual genes was documented in a study in healthy young adults. Exposure-effect relations were reserved in which the response often turned out to be gender-specific. The technology can be used in a biomonitoring context as an "early warning signal" for complex exposure, but the interpretation of the meaning for health requires further follow-up.

Publication year:2011

Accessibility:Open