Reduced expression of von Hippel–Lindau gene in subjects exposed to polychlorinated biphenyls and dibenzofurans

Abstract: Polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) are ubiquitous pollutants found in the environment and human tissues. A cohort in Taiwan has undergone follow-up for 24 years after exposure to high levels of PCBs and PCDFs. The incidence of chloracne, hyperkeratosis, and abnormal nail was increased among exposed people. We conducted a study to identify the genes whose expressions were affected by such exposure. A cDNA microarray system consisting of 908 genes was used for pooled serum samples from non-smoking men exposed to PCBs and PCDFs (n=15) and their matched referents (n=15) in triplicate. After adjusting for background and housekeeping genes, genes with different expressions between the exposure and reference groups were determined by both regression and cluster analysis, and further confirmed by real-time RT-PCR. The tumor suppressor gene von Hippel–Lindau (VHL) was found to be down-regulated in the microarray analysis. VHL gene expression levels were also found to be positively associated with age, shown by real-time RT-PCR. Upon age adjustment, VHL gene expression was reduced in Yucheng (“oil disease”) subjects as compared to referents. Among Yucheng people, those with abnormal nails had lower VHL expressions than those without abnormal nails. These findings provide new insights into the potential role of VHL in health conditions associated with PCB and PCDF exposures. [Copyright &y& Elsevier]