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Lack of Association Between Two Restriction Fragment Length Polymorphisms in the Genes for the Light and Heavy Neurofilament Proteins and Alzheimer's Disease

Published online by Cambridge University Press:  18 September 2015

Ginette Lacoste-Royal ,
Martine Mathieu ,
Josephine Nalbantoglu ,
Jean-Pierre Julien ,
Serge Gauthier  and
Denis Gauvreau
Ginette Lacoste-Royal*
Affiliation:
INRS-Santé, Pointe-Claire, Montréal
Martine Mathieu
Affiliation:
INRS-Santé, Pointe-Claire, Montréal
Josephine Nalbantoglu
Affiliation:
INRS-Santé, Pointe-Claire, Montréal
Jean-Pierre Julien
Affiliation:
Institut de Cancer de Montréal, Montréal
Serge Gauthier
Affiliation:
Centre McGill d'études sur le vieillissement, Montréal
Denis Gauvreau
Affiliation:
INRS-Santé, Pointe-Claire, Montréal
*
INRS-Santé, 245 boul. Hymus, Point-Claire, Quebec, Canada H9R 1G6
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Abstract:

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The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a Taql-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. Hindi detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

Résumé:

RÉSUMÉ:

La cause de la maladie d'Alzheimer (MA) demeure inconnue. L'hypothèse que des facteurs génétiques jouent un rôle dans la maladie, du moins dans sa forme familiale, a été confirmée dans un ensemble de quatre familles MA à début précoce, où un linkage a été démontré entre la maladie et un locus situé sur la partie proximale du bras long du chromosome 21. Il n'a pas été possible de déceler ce linkage dans plusieurs autres familles MA, en utilisant les mêmes marqueurs. Le métabolisme des neurofilaments est perturbé dans la MA, comme en témoignent la présence d'épitopes de neurofilaments dans les enchevêtrements neurofibrillaires, et la baisse substantielle d'expression du gène pour la petite sousunité des neurofilaments dans le cerveau affecté par la maladie. Afin de détecter une anomalie possiblement reliée à la MA, nous avons cherché s'il y avait une association entre les gènes pour la petite et la grosse sour-unités des neurofilaments et la MA. Les génotypes pour des polymorphismes dans la taille des fragments de restriction à chacun des deux loci ont été déterminés dans un groupe contrôle et un groupe MA. Les fréquences alléliques pour un polymorphisme Taql dans le gène de la petite sous-unité des neurofilaments sont de 0.7 pour l'allèle de 3.7 kb et 0.3 pour l'allèle de 2.9 kb. HincII détecte un polymorphisme dans le gène de la grosse sous-unité des neurofilaments, avec des fréquences de 0.31 pour l'allèle de 18.0 kb et 0.69 pour l'allèle de 6.8 kb. Les fréquences alléliques sont similaires dans les deux groupes pour les deux loci examinés. Ces résultats ne supportent pas une association entre les gènes des neurofilaments et la MA, quoiqu'on ne puisse exclure une mutation à un autre site.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 17 , Issue 3 , August 1990 , pp. 302 - 305
Copyright
Copyright © Canadian Neurological Sciences Federation 1990

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