Article

Slow allotypic variants of the NAT2 gene and susceptibility to early-onset Parkinson's disease.

Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Neurology (impact factor: 8.31). 01/1999; 51(6):1587-92. pp.1587-92
Source: PubMed

ABSTRACT To determine the frequency and the linkage distribution of seven mutations at the polymorphic gene coding for the arylamine N-acetyl transferase (NAT2; EC 2.3.1.5) in 121 unrelated patients with sporadic PD and in 121 unrelated healthy volunteers.
The study was performed with mutation-specific PCR using genomic DNA obtained from blood of the probands.
Comparison of the NAT2 genotypes of the overall PD patients and control subjects did not indicate statistically significant differences. However, patients with early-onset PD (onset before the age of 50 years, n=37) showed a higher frequency of slow-acetylation genotypes (78.4% patients) compared with both healthy control subjects (55.4%) and with late-onset (onset after 51 years of age, n=84) PD patients (54.8%). Such a difference was statistically significant (p < 0.015) and was the result of a homogeneous increase in the frequency of slow-acetylation alleles. All subgroups analyzed in the study were in Hardy-Weinberg equilibrium for mutations at the NAT2 gene.
Slow-acetylation-mutated alleles may be considered low-penetrance genes in early-onset PD pathogenesis, with a relative risk ratio for individuals with slow-acetylation genotype of 2.92 (95% CI, 1.26 to 6.78). This study provides evidence for the interaction of genetic and environmental factors in the etiology of sporadic PD.

0 0
 · 
0 Bookmarks
 · 
27 Views
  • Source
    Article: N-acetyltransferase-2 polymorphisms and schizophrenia.
    Pilar Alejandra Saiz, Maria P Garcia-Portilla, Celso Arango, Blanca Morales, Victoria Alvarez, Eliecer Coto, Juan M Fernandez, Manuel Bousono, Julio Bobes
    European Psychiatry 08/2006; 21(5):333-7. · 2.77 Impact Factor
  • Source
    Article: N-acetyltransferase polymorphisms and colorectal cancer: a HuGE review.
    N Brockton, J Little, L Sharp, S C Cotton
    [show abstract] [hide abstract]
    ABSTRACT: The two expressed genes coding for N-acetyltransferase (NAT) activity, NAT1 and NAT2, are located on chromosome 8 at 8p21.3-23.1 and are polymorphic. Both enzymes are capable of N-acetylation, O-acetylation, and N,O-acetylation and are implicated in the activation and detoxification of known carcinogens. Single base-pair substitutions in NAT2 tend to occur in combination with other substitutions within the gene. As yet, less work has been done to characterize NAT1 allelic variants. Various methods for the detection of the reported polymorphisms exist. It is important to select a method that is appropriate to the population being studied. The functional significance of many NAT allelic variants has not been determined. Geographic and ethnic variation in the frequency of NAT2 genotypes associated with fast or intermediate acetylation has been observed. Insufficient data for NAT1 genotypes are available to reveal a clear geographic pattern. No consistent association has been found between acetylator phenotype or genotype and colorectal cancer. The lack of consistency can in part be accounted for by methodological factors, including limited statistical power. Possible interactions between the NAT genes and either environmental exposures or other polymorphic genes encoding xenobiotic metabolizing enzymes have been investigated in only a minority of these studies, and these studies have lacked statistical power to detect interactions.
    American Journal of Epidemiology 06/2000; 151(9):846-61. · 5.22 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

121 unrelated healthy volunteers
 
121 unrelated patients
 
arylamine N-acetyl transferase
 
control subjects
 
early-onset PD
 
early-onset PD pathogenesis
 
Hardy-Weinberg equilibrium
 
healthy control subjects
 
higher frequency
 
homogeneous increase
 
low-penetrance genes
 
mutation-specific PCR
 
NAT2 gene
 
NAT2 genotypes
 
PD patients
 
polymorphic gene coding
 
relative risk ratio
 
slow-acetylation genotype
 
sporadic PD
 
statistically significant differences