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NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant
BACKGROUND: Alzheimer's disease is multifactorial, having environmental, toxicological and genetic risk factors. Impaired folate and homocysteine metabolism has been hypothesised to increase risk. In addition to its xenobiotic-metabolising capacity, human arylamine N-acetyltransferase type-1 (N...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2004
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395831/ https://www.ncbi.nlm.nih.gov/pubmed/15142281 http://dx.doi.org/10.1186/1471-2350-5-6 |
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author | Johnson, Nichola Bell, Peter Jonovska, Vesna Budge, Marc Sim, Edith |
author_facet | Johnson, Nichola Bell, Peter Jonovska, Vesna Budge, Marc Sim, Edith |
author_sort | Johnson, Nichola |
collection | PubMed |
description | BACKGROUND: Alzheimer's disease is multifactorial, having environmental, toxicological and genetic risk factors. Impaired folate and homocysteine metabolism has been hypothesised to increase risk. In addition to its xenobiotic-metabolising capacity, human arylamine N-acetyltransferase type-1 (NAT1) acetylates the folate catabolite para-aminobenzoylglutamate and is implicated in folate metabolism. The purpose of this study was to determine whether polymorphisms in the human NAT genes influence susceptibility to Alzheimer's disease. METHODS: Elderly individuals with and without Alzheimer's disease were genotyped at the polymorphic NAT1 (147 cases; 111 controls) and NAT2 (45 cases; 63 controls) loci by polymerase chain reaction-restriction fragment length polymorphism, and the genotype and allele frequencies were compared using the chi-squared test. RESULTS: Although a trend towards fast NAT2 acetylator-associated Alzheimer's disease susceptibility was indicated and the NAT1*10/1*10 genotype was observed only in cases of Alzheimer's disease (6/147, 4.1%), no significant difference in the frequency of NAT2 (p = 0.835) or NAT1 (p = 0.371) genotypes was observed between cases and controls. In addition, a novel NAT1 variant, NAT1*11B, was identified. CONCLUSIONS: These results suggest that genetic polymorphisms in NAT1 and NAT2 do not influence susceptibility to Alzheimer's disease, although the increase in frequency of the NAT1*10 allele in Alzheimer's disease is worthy of further investigation. Due to its similarity with the NAT1*11A allele, NAT1*11B is likely to encode an enzyme with reduced NAT1 activity. |
format | Text |
id | pubmed-395831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-3958312004-04-25 NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant Johnson, Nichola Bell, Peter Jonovska, Vesna Budge, Marc Sim, Edith BMC Med Genet Research Article BACKGROUND: Alzheimer's disease is multifactorial, having environmental, toxicological and genetic risk factors. Impaired folate and homocysteine metabolism has been hypothesised to increase risk. In addition to its xenobiotic-metabolising capacity, human arylamine N-acetyltransferase type-1 (NAT1) acetylates the folate catabolite para-aminobenzoylglutamate and is implicated in folate metabolism. The purpose of this study was to determine whether polymorphisms in the human NAT genes influence susceptibility to Alzheimer's disease. METHODS: Elderly individuals with and without Alzheimer's disease were genotyped at the polymorphic NAT1 (147 cases; 111 controls) and NAT2 (45 cases; 63 controls) loci by polymerase chain reaction-restriction fragment length polymorphism, and the genotype and allele frequencies were compared using the chi-squared test. RESULTS: Although a trend towards fast NAT2 acetylator-associated Alzheimer's disease susceptibility was indicated and the NAT1*10/1*10 genotype was observed only in cases of Alzheimer's disease (6/147, 4.1%), no significant difference in the frequency of NAT2 (p = 0.835) or NAT1 (p = 0.371) genotypes was observed between cases and controls. In addition, a novel NAT1 variant, NAT1*11B, was identified. CONCLUSIONS: These results suggest that genetic polymorphisms in NAT1 and NAT2 do not influence susceptibility to Alzheimer's disease, although the increase in frequency of the NAT1*10 allele in Alzheimer's disease is worthy of further investigation. Due to its similarity with the NAT1*11A allele, NAT1*11B is likely to encode an enzyme with reduced NAT1 activity. BioMed Central 2004-03-17 /pmc/articles/PMC395831/ /pubmed/15142281 http://dx.doi.org/10.1186/1471-2350-5-6 Text en Copyright © 2004 Johnson et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Article Johnson, Nichola Bell, Peter Jonovska, Vesna Budge, Marc Sim, Edith NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant |
title | NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant |
title_full | NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant |
title_fullStr | NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant |
title_full_unstemmed | NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant |
title_short | NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant |
title_sort | nat gene polymorphisms and susceptibility to alzheimer's disease: identification of a novel nat1 allelic variant |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395831/ https://www.ncbi.nlm.nih.gov/pubmed/15142281 http://dx.doi.org/10.1186/1471-2350-5-6 |
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