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Cytochrome P450 1A1 and 1A2 CYP1A1/CYP1A2 [T88.7]

OMIM numbers: 108330 (CYP1A1), 124060 (CYP1A2)

Dipl.-Biol. Birgit Busse

Scientific Background

CYP1A1: Cytochrome P450-1A1 (CYP1A1) belongs to the group of phase I enzymes and facilitates the metabolism of environmental toxins such as polycyclic aromates (e.g. toxification of benzpyrenes) and various xenobiotics. The constitutive expression of the enzyme is low; yet, it can be induced significantly by polycyclic aromatic hydrocarbons (PAHs). Two frequently occurring polymorphisms (T3801C and A2455C) have been associated with an increased inducibility and thus with an increased activity of the enzyme. Approximately 10% of the Caucasian population carries these polymorphisms. 

CYP1A2: Cytochrome P450-1A2 is involved in the metabolism of various drugs and environmental toxins. Certain variants in the CYP1A2 gene are known to lead to changes in the enzyme activity. The enzyme can be induced by various substances (e.g. cigarette smoke). Especially the CYP1A2*1F allele has been associated with a higher inducibility and increased substrate metabolism. This allele has a frequency of 70% in the Caucasian population. Besides various drugs, substrates of CYP1A2 are aromatic and heterocyclic amines. Since the clinical relevance of the genetic variants has not entirely been clarified yet, the analysis of the gene is currently not part of routine diagnostics and is only conducted after consultation.

The metabolism of xenobiotics in the body usually involves several steps with several enzyme systems being involved. In the intermediate stages of the detoxification process, toxic metabolites can occur. In many cases, the route of degradation with all its enzyme systems involved has not entirely been characterized yet. Therefore, the analysis of the CYP1A1 and the CYP1A2 genotype only provides partial information on the toxification capacity of the patient.