Cytochrome P450 1A1 (CYP1A1) gene in familial and sporadic idiopathic Parkinson's disease (IPD)

Abstract

The CYPlA1 gene Is expressed in brain, and its product, P450 1A1, catalyses the oxidation of MPTP to MPDP'. and then to MPP'. CYPlA1 Is polymorphlc and one pdymophism (locus 1; T common: C rare: absence or presence of a Msp I site) has been associated with an Increased risk of lung cancer (Hayashi S et al. J. Blochern. 1991;110:407411). A second polymorphism (locus 2; A common: G rare) causes an amino acM substitution in the haem bindlng site of P450 1Al (Hayashi. S et al. Nudelc Acld Res. 1991;19:4797). W6determined aliellc frequencles at these loci uslng PCR-based methods in 49 healthy controls, 50 sporadic IPD patients, and 8 famllhl IPD klndreds. No significant daferences in aildlc frequencies were found between controls and sporadic IPD patlents at either locus. However. the rare allele at locus 2 was slgnlficantiy over-represented in the affected familial IPD Index patients (2 out of 8) compared with controls (1 out of 50: p< 0.008). No slgnificant differences in locus 2 allelic frequencles were found between unaffected IPD family members and controls, or in allelic frequencles at locus 1 among any groups. Abnormal metabolism of xenoblotica by a rare lsoform of P450 1Al may be a signfflcant factor for the development of familial IPD in certain klndreds.