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N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease
BACKGROUND: Parkinson'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 varia...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450268/ https://www.ncbi.nlm.nih.gov/pubmed/16571112 http://dx.doi.org/10.1186/1471-2350-7-30 |
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author | Borlak, Juergen Reamon-Buettner, Stella Marie |
author_facet | Borlak, Juergen Reamon-Buettner, Stella Marie |
author_sort | Borlak, Juergen |
collection | PubMed |
description | BACKGROUND: Parkinson'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. METHODS: We 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. RESULTS: Overall, 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. CONCLUSION: We 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. |
format | Text |
id | pubmed-1450268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-14502682006-04-29 N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease Borlak, Juergen Reamon-Buettner, Stella Marie BMC Med Genet Research Article BACKGROUND: Parkinson'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. METHODS: We 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. RESULTS: Overall, 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. CONCLUSION: We 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. BioMed Central 2006-03-29 /pmc/articles/PMC1450268/ /pubmed/16571112 http://dx.doi.org/10.1186/1471-2350-7-30 Text en Copyright © 2006 Borlak and Reamon-Buettner; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Borlak, Juergen Reamon-Buettner, Stella Marie N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease |
title | N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease |
title_full | N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease |
title_fullStr | N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease |
title_full_unstemmed | N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease |
title_short | N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease |
title_sort | n-acetyltransferase 2 (nat2) gene polymorphisms in parkinson's disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1450268/ https://www.ncbi.nlm.nih.gov/pubmed/16571112 http://dx.doi.org/10.1186/1471-2350-7-30 |
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