The M694V Variant of the Familial Mediterranean Fever Gene Is Associated with Sporadic Early-Onset Alzheimer’s Disease in an Italian Population SampleArra M. · Emanuele E. · Martinelli V. · Minoretti P. · Bertona M. · Geroldi D.
Background: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. Methods: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. Results: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24–6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34–1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). Conclusion: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.
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