PMID- 9170146
OWN - NLM
STAT- MEDLINE
DCOM- 19970729
LR  - 20191024
IS  - 0960-314X (Print)
IS  - 0960-314X (Linking)
VI  - 7
IP  - 2
DP  - 1997 Apr
TI  - Human Ah receptor (AHR) gene: localization to 7p15 and suggestive correlation of 
      polymorphism with CYP1A1 inducibility.
PG  - 95-101
AB  - The mammalian aromatic hydrocarbon receptor (AHR) is a ubiquitous 
      ligand-activated transcription factor. AHR ligands include 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin), benzo[a]pyrene, and 
      polychlorinated and polybrominated biphenyls; the endogenous ligand is not yet 
      known. Following ligand binding, the AHR transcriptionally activates genes 
      encoding drug-metabolizing enzymes important in both the metabolic potentiation 
      of substrates to genotoxic reactive intermediates and ultimate carcinogens, and 
      the detoxification of toxic or carcinogenic drugs and other environmental 
      pollutants. AHR-mediated gene expression is also involved in many critical life 
      processes (e.g. cell type-specific differentiation, cell division, apoptosis) by 
      signal transduction mechanisms. Similar to mice, human populations exhibit a > 
      20-fold range of the CYP1A1 inducibility/AHR affinity phenotype. In the present 
      study, we localized the human AHR gene to chromosome 7p15, using fluorescence in 
      situ hybridization (FISH). Performing linkage analysis in a three-generation 
      family, we show with good probability that the high CYP1A1 inducibility phenotype 
      segregates with the 7p15 region. Sequencing 93 nt (31 amino acids) of the human 
      AHR gene's exon 9, which is the region correlated with the mouse A375V 
      polymorphism responsible for the major portion of high vs low CYP1A1 
      inducibility/AHR affinity, we found no nucleotide differences; Val-381 was 
      present in all five individuals examined (four related and one unrelated), two of 
      whom show "high' and three of whom show "low' CYP1A1 inducibility. These data 
      indicate that the "high' and "low' CYP1A1 inducibility trait, in the population 
      studied, cannot be explained by a difference among these 31 amino acids in exon 9 
      of the AHR gene.
FAU - Micka, J
AU  - Micka J
AD  - Physician Scientist Training Program, CHRF, Cincinnati, OH 45229, USA.
FAU - Milatovich, A
AU  - Milatovich A
FAU - Menon, A
AU  - Menon A
FAU - Grabowski, G A
AU  - Grabowski GA
FAU - Puga, A
AU  - Puga A
FAU - Nebert, D W
AU  - Nebert DW
LA  - eng
GR  - P30 ES06096/ES/NIEHS NIH HHS/United States
GR  - R01 ES06273/ES/NIEHS NIH HHS/United States
GR  - R01 ES06811/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Pharmacogenetics
JT  - Pharmacogenetics
JID - 9211735
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 7
MH  - Cytochrome P-450 CYP1A1/*biosynthesis
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lod Score
MH  - Male
MH  - Molecular Sequence Data
MH  - Pedigree
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Receptors, Aryl Hydrocarbon/*genetics
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1097/00008571-199704000-00002 [doi]
PST - ppublish
SO  - Pharmacogenetics. 1997 Apr;7(2):95-101. doi: 10.1097/00008571-199704000-00002.