title: Genetic susceptibility to dioxin-like chemicals' induction of cytochrome P4501A2 in the human adult linked to specific AhRR polymorphism.
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental and Occupational Medicine, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Hung
authors.forename: George H
authors.initials: GH
authors.lastname: Lambert
authors.forename: Ping-Wei
authors.initials: PW
authors.lastname: Huang
authors.forename: Donald G
authors.initials: DG
authors.lastname: Patterson
authors.forename: Yue Leon
authors.initials: YL
authors.lastname: Guo
mesh_terms: D000328:Adult; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D004147:Dioxins / Q000506:poisoning / Q000633:toxicity*; D004785:Environmental Pollutants / Q000506:poisoning / Q000633:toxicity*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004147:Dioxins; D004785:Environmental Pollutants; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019388:Cytochrome P-450 CYP1A2