Purpose: Fragile X-associated tremor/ataxia syndrome is a late-onset neurodegenerative disorder that occurs in FMR1 premutation carriers. It is well known that the apolipoprotein E ε4 allele is a risk factor for neurodegenerative disease. The main goal of this work was to evaluate the apolipoprotein E genotypes and allelic distribution among patients with fragile X-associated tremor/ataxia syndrome.
Methods: A total of 44 unrelated FMR1 premutation carriers (22 presenting with fragile X-associated tremor/ataxia syndrome and 22 without fragile X-associated tremor/ataxia syndrome) were genotyped.
Results: All the apolipoprotein E ε4/4 genotype carriers detected (100%), and six of the seven apolipoprotein E ε4/3 genotype carriers (85.7%) are patients presenting with fragile X-associated tremor/ataxia syndrome symptoms, whereas only 40% of the apolipoprotein E ε3/3 genotype carriers belong to the fragile X-associated tremor/ataxia syndrome group. The results showed that the presence of the apolipoprotein E ε4 allele increases the risk of developing fragile X-associated tremor/ataxia syndrome (odds ratio = 12.041; P = 0.034).
Conclusion: On the basis of these results, we conclude that the presence of at least one apolipoprotein E ε4 allele might act as a genetic factor predisposing individuals to develop fragile X-associated tremor/ataxia syndrome.