N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease.

Juergen Borlak,Stella Marie Reamon-Buettner

doi:10.1186/1471-2350-7-30

Juergen Borlak, Stella Marie Reamon-Buettner

Open Access

https://doi.org/10.1186/1471-2350-7-30

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Abstract

BackgroundParkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.MethodsWe analyzed three NAT2 genetic variations, c.481C>T, c.590G>A (p.R197Q) and c.857G>A (p.G286E), which are known to result in a slow acetylator phenotype. Using validated PCR-RFLP assays, we genotyped 243 healthy unrelated Caucasian control subjects and 124 PD patients for these genetic variations. Further, we have undertaken a systematic review of NAT2 studies on PD and we incorporated our results in a meta-analysis consisting of 10 studies, 1,206 PD patients and 1,619 control subjects.ResultsOverall, we did not find significant differences in polymorphic acetylation genotypes in PD and control subjects. In the meta-analysis of slow acetylators from 10 studies and representing 604/1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 (95% CI 1.12–1.54, p < 0.05) was obtained. Re-analysis of the data to exclude the only two studies showing positive association of slow acetylators to PD, resulted in a non-significant OR (1.07, 95% CI 0.9–1.28). Furthermore, meta-analysis of studies for c.590G>A, where both allele and genotype frequencies in PD vs. control subjects were analyzed, did not give significant summary odds ratios as well.ConclusionWe found little evidence for differences in polymorphic acetylation genotypes in PD and control subjects. Results of the meta-analyses did not also provide conclusive evidence for an overall association of NAT2 slow acetylator genotypes to PD.

Highlights

Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain
In the meta-analysis of slow acetylators from 10 studies and representing 604/ 1206 PD vs. 732/1619 control subjects, a marginally significant odds ratio (OR) of 1.32 was obtained
While homozygotes for c.481C>T did not differ in control and PD, homozygotes for c.590G>A were more frequent in control

Summary

Introduction

Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. Parkinson's disease (PD, MIM #16860) is a progressive neurodegenerative disorder characterized by resting tremor, muscular rigidity, bradykinesia (slowness of movement), postural instability, and pathologically, the presence of Lewy bodies This movement disorder is caused by a deficiency of the neurotransmitter dopamine in the striatum of the brain, as a result of degenerating (page number not for citation purposes). A collaborative pooled analysis of 11 published studies of the UCHL1 p.S18Y variant involving 1,970 PD cases and 2,224 unrelated controls, confirmed an inverse association between this variant and PD in younger subjects [3] Neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amine-related neurotoxins are proposed to be among the environmental factors, killing selectively dopaminergic neurons over a long period of time [4]

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