Genetics

Poster Session 1 - TICSThe 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