Abstract：
BACKGROUND:Dioxin-like chemicals are known to exert their effect by binding to aryl hydrocarbon receptor (AhR), forming complexes with aryl hydrocarbon nuclear translocator (ARNT), and binding to dioxin responsive elements (DREs) in promoter region to regulate the transcription of specific genes. In a previous study of the Yucheng cohort of humans who were exposed to high toxic levels of dioxin-like chemicals (PCDFs and PCBs), we reported marked induction of cytochrome P450 1A2 (CYP1A2) activity and this induction was an excellent biomarker of the exposure and adverse human health effects seen in the Yucheng cohort. OBJECTIVES:The goal of this study was to determine the relationship between inducibility of CYP1A2 and genetic polymorphisms of AhR, ARNT, and AhRR in human. METHODS:The Yucheng victims who completed blood sample collecting in 1994-1995 for serum concentrations of PCB, PCDF, and PCDD congeners, and also completed the caffeine breath tests for CYP1A2 activity were identified. From the collected blood samples, six single nucleotide polymorphisms were selected for genotyping, including AhR (rs2066853), AhRR (rs2292596), ARNT (rs7517566), ARNT (rs3820541), ARNT (rs3768016), and ARNT (rs2228099). RESULTS:AhRR (rs2292596) polymorphism was significantly related to CYP1A2 inducibility (p=0.01). A linear trend test was observed between people with AhRR (rs2292596) GG, GC, and CC genotype (p=0.0014). CONCLUSION:Overall, AhRR (rs2292596) genotypes predict the inducibility of CYP1A2 in people highly exposed to toxic dioxin-like chemicals. Future studies and analysis will determine to what degree these polymorphisms can predict a human's susceptibility to dioxin-related adverse human health effects.
journal_name
Chemospherejournal_title
Chemosphereauthors
Hung WT,Lambert GH,Huang PW,Patterson DG Jr,Guo YLdoi
10.1016/j.chemosphere.2012.10.026subject
Has Abstractpub_date
2013-03-01 00:00:00pages
2358-64issue
9eissn
0045-6535issn
1879-1298pii
S0045-6535(12)01265-9journal_volume
90pub_type
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