Apolipoprotein E and presenilin-1 genotypes in Huntington’s disease

Huntington’s disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer’s disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20–65) we determined number of CAG repeats and the distribution of the APOE alleles (ɛ2, ɛ3, ɛ4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the ɛ4 allele (51.6 vs. 38.0 P < 0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the ɛ3/ɛ3 genotype while it was not detected in patients with ɛ3/ɛ4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington’s disease.