The role of NAT2 gene polymorphism in aetiology of the most frequent neurodegenerative diseases with dementia

Abstract

Background and purpose: The role of N-acetyltransferase gene (NAT2) polymorphism in the aetiology of Alzheimer's disease (AD) and Parkinson's disease (PD) is an interesting issue; it is suggested that the slow acetylator genotype favours the damage of central nervous system cells by environmental toxins. The aims of the study were: 1) to determine the genotype of NAT2 in patients with sporadic PD with dementia and in patients with sporadic AD; 2) to evaluate the relationship between the genotype of NAT2 and the age at the onset of the disease, the extent of dementia, and the dose and side effects of L-dopa (in PD patients only); 3) to evaluate the predispositions to PD and AD.

Material and methods: Fifty two PD patients with dementia aged 51-82 years (mean: 70.35) and 53 AD patients aged 58-84 years (mean: 72.58) were recruited. The control group consisted of 90 healthy subjects aged 65-86 years (mean: 72.11). Four standardized instruments for evaluation of dementia in PD patients were used. Clinical scales for PD evaluation were used. Each AD patient satisfied the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable AD. Methods of molecular biology were used for genetic studies.

Results: The NAT2*5/NAT2*5 genotype was more frequent in PD patients with dementia; the NAT2*4/NAT2*5 genotype was more frequent and the NAT2*4/NAT2*6 genotype was less frequent in AD patients. No relationship was found between genotypes and NAT2 alleles and the age at onset, severity of dementia or with the dose and side effects of L-dopa (in PD patients).

Conclusions: The analysis of NAT2 polymorphism does not seem to be useful in predicting the risk of PD with dementia or AD.