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


METHODS
The study was performed with mutation-specific PCR using genomic DNA obtained from blood of the probands.


RESULTS
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.


CONCLUSIONS
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.
Agúndez
J A
JA
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Jiménez-Jiménez
F J
FJ
Luengo
A
A
Molina
J A
JA
Ortí-Pareja
M
M
Vázquez
A
A
Ramos
F
F
Duarte
J
J
Coria
F
F
Ladero
J M
JM
Alvarez-Cermeño
J C
JC
Benítez
J
J
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D011110:Polymorphism, Genetic
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human