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Slow Acetylation Genotype may Contribute to PD
Source: Bandmann O, et al. Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson's disease. Lancet 1997;350:1136-1139.
Bandmann and colleagues performed a genetic analysis of six detoxification enzymes in blood samples of 100 patients with familial Parkinson's disease (PD), brain tissue from 100 patients with pathologically proven sporadic PD, and 100 normal brains, or blood from 100 patients with Huntington's disease. The six enzymes studied, with PCR-based methods and restriction enzyme analysis to detect genetic polymorphisms, were CYP2D6, CYP2E1, NAD(P)H-menadione reductase, glutathione transferases M1 and T1, and N-acetyltranferase 2.
The slow acetylator genotype for N-acetyltransferase 2 was significantly more common in the familial PD (69%) than in controls (37%; P = 0.002). The proportion of the sporadic PD with slow acetylators was also higher (59%), but only trended toward significance (P = 0.06). The frequencies of other enzyme polymorphisms were similar in all groups.
COMMENTARY
Increasing evidence arises for the involvement of genetic factors in the pathogenesis of PD, with several large family pedigrees of autosomal dominantly inherited PD, and the first genetic locus mapped to 4q21-23 in one such family (Polmeropoulos M, et al. Science 1996;274:1197-1199). Other identified risk factors, such as environmental exposure to toxins such as organochlorines and alkylated phosphates, may play a role. Thus, a genetic predisposition, such as the slow acetylator genotype for N-acetyltransferase 2, could lead to impaired ability to handle neurotoxic substances. Further studies are needed to clarify the role of slow acetylation in this neurodegenerative disorder and may lead to additional therapeutic strategies. -ba
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