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NEUROLOGY 1998;51:1587-1592
© 1998 American Academy of Neurology

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

J.A.G. Agúndez, MD, PhD, F. J. Jiménez-Jiménez, MD, PhD, A. Luengo, MD, PhD, J. A. Molina, MD, PhD, M. Ortí-Pareja, MD, PhD, A. Vázquez, MD, F. Ramos, MD, J. Duarte, MD, F. Coria, MD, PhD, J. M. Ladero, MD, PhD, J. C. Alvarez-Cermeño, MD, PhD and J. Benítez, MD, PhD

From the Department of Pharmacology (Drs. Agúndez and Benítez), Medical School, University of Extremadura, Badajoz; Section of Neurology (Drs. Jiménez-Jiménez and Ortí-Pareja), University Hospital Principe de Asturias, Alcalá de Henares, Madrid; Service of Neurology (Drs. Luengo and Ramos), Hospital de la Princesa, Madrid; Service of Neurology (Dr. Molina), Hospital Doce de Octubre, Madrid; Services of Neurology and Gastroenterology (Drs. Vázquez and Ladero), University Hospital San Carlos, Madrid; Service of Neurology (Dr. Duarte), General Hospital, Segovia; Service of Neurology (Dr. Coria), Hospital Del Rio Hortega, Valladolid; and Service of Neurology (Dr. Cermeño), Hospital Ramón y Cajal, Madrid, Spain.

Address correspondence and reprint requests to Prof. Julio Benítez, Departamento de Farmacología, Facultad de Medicina, Universidad de Extremadura, Avda. de Elvas s/n, 06071-Badajoz, Spain.

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.

Supported in part by grants CICYT-SAF96-0006 from Comision Interministerial de Ciencia y Technología; UE95-0043 and UE97-0001 from Secretaría de Estado de Universidades, Investigación y Desarrollo (Madrid, Spain); FISss 94/0326, 97/1262, and 98/5036 from Fondo de Investigaciones Sanitarias de la Seguridad Social (Madrid, Spain); BMH1-CT94-1622 and BMH4-CT96-0291 from the European Union; and PRI96060023 and PRI97C120 from Junta de Extremadura (Merida, Spain).

Received April 8, 1998. Accepted in final form August 14, 1998.




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