Format

Send to

Choose Destination
See comment in PubMed Commons below
Lancet. 1997 Oct 18;350(9085):1136-9.

Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson's disease.

Author information

1
University Department of Clinical Neurology, Institute of Neurology, London, UK.

Abstract

BACKGROUND:

Epidemiological studies have identified positive family history and exposure to environmental toxins as risk factors for Parkinson's disease (PD). An inherited defect of xenobiotic metabolism could result in increased susceptibility to such toxins. We investigated the frequency of functionally relevant polymorphisms in six detoxification enzymes among patients with PD to elucidate the relation between these polymorphisms and the disease.

METHODS:

We obtained brain-tissue samples from 100 patients with apparently sporadic PD and blood samples from 100 living patients with familial PD. For the control group, we extracted DNA from the tissue of 100 pathologically normal brains. The six enzymes analysed in these three groups were: CYP2D6, CYP2E1, NAD(P)H-menadione reductase, glutathione transferases M1 and T1, and N-acetyltransferase 2. We also investigated N-acetyltransferase 2 in 100 blood samples from patients with genetically proven Huntington's disease. We used PCR-based methods and restriction-enzyme analysis to detect polymorphisms.

FINDINGS:

The slow acetylator genotype for N-acetyltransferase 2 was more common in the familial PD group (69%) than in all controls (37%). Even after correction for multiple comparisons, this result remained highly significant (p = 0.002) for familial PD compared with normal controls (odds ratio 3.79 [95% CI 2.08-6.90]) and compared with Huntington's disease (2.45 [1.37-4.38], p = 0.004). The slow acetylator frequency for N-acetyltransferase 2 for sporadic PD was between that for Huntington's disease and familial PD. The frequencies of all the other polymorphisms were similar in the two study groups and the normal control group.

INTERPRETATION:

We found an association between the slow acetylator genotype for N-acetyltransferase 2 and familial PD. Further studies are needed to investigate the biological relevance of these findings, but slow acetylation could lead to impaired ability of patients with familial PD to handle neurotoxic substances.

PMID:
9343502
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center