APOE ε4 allele is associated with an increased risk of bulbar-onset amyotrophic lateral sclerosis in men - PubMed (original) (raw)
APOE ε4 allele is associated with an increased risk of bulbar-onset amyotrophic lateral sclerosis in men
J Praline et al. Eur J Neurol. 2011 Aug.
Abstract
Objective: Several association studies have identified possible susceptibility factors for sporadic amyotrophic lateral sclerosis (SALS). Studies on the APOE gene provided conflicting results, especially about the effect on bulbar onset. We assessed the possible role of APOE gene in a large cohort of patients with ALS and matched controls.
Methods: The APOE alleles were determined in 1482 patients with SALS and 955 controls and analysed by univariate and multivariate statistics, taking into account gender, site-of-onset and age-at-onset.
Results: Patients with bulbar onset were more likely to be women [odds ratio (OR)=2.17; 95% CI: 1.74-2.72] and to be older (OR=3.47; 95% CI: 2.58-4.67). The ε4-carriers were more frequent in the bulbar-onset group than in the limb-onset group (OR=1.39 bulbar onset versus limb onset; 95% CI: 1.08-1.80) but this association was observed amongst men (OR=1.78; 95% CI: 1.25-2.53) and not women (OR=1.09; 95% CI: 0.75-1.59).
Conclusion: Our study provides evidence for a contribution of the ε4 allele in the occurrence of bulbar-onset ALS amongst men. We propose that men are normally protected by androgens against bulbar onset and that the ε4 allele inhibits this protection, perhaps by interfering with the androgen pathway.
© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.
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