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Association of early‐onset Alzheimer's disease with an interleukin‐1α gene polymorphism
Author(s) -
Grimaldi Luigi M. E.,
Casadei Valeria M.,
Ferri Cinzia,
Veglia Fabrizio,
Licastro Federico,
Ani Giorgio,
Biunno Ida,
De Bellis Gianluca,
Sorbi Sandro,
Mariani Claudio,
Canal Nicola,
Griffin W. Sue T.,
Franceschi Massimo
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200003)47:3<361::aid-ana12>3.0.co;2-n
Subject(s) - genotype , disease , age of onset , locus (genetics) , odds ratio , genetic association , alzheimer's disease , immunology , biology , genetics , medicine , gene , pathology , single nucleotide polymorphism
Overexpression of the pluripotent cytokine interleukin‐1 (IL‐1) by microglial cells correlates with formation of neuritic β‐amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL‐1α, IL‐1β, and IL‐1 receptor antagonist cytokines, and tested their association with the occurrence and age at onset of sporadic AD. We found a strong association between the IL‐1A T/T genotype and AD onset before 65 years of age (odds ratio, 4.86), with carriers of this genotype showing an onset of disease 9 years earlier than IL‐1A C/C carriers. A weaker association with the age at onset was also shown for the IL‐1B and IL‐1RN genes. These data suggest either a direct effect of the IL‐1 gene family, mainly IL‐1A, on the clinical onset of AD, or a linkage dysequilibrium with an unknown locus relevant to AD on chromosome 2. Ann Neurol 2000;47:361–365