Interleukin-1B polymorphism is associated with age at onset of Alzheimer's disease.
Interleukin-1alpha (IL-1alpha) and IL-1beta are two pro-inflammatory cytokines involved in the pathogenesis of Alzheimer's disease (AD). The genes coding for IL-1alpha (IL-1A) and for IL-1beta (IL-1B) are clustered in chromosome 2q14-2q14.2. In a previous work, we investigated the role of IL-1A promoter polymorphism (-889 position) in AD pathogenesis: IL-1A -889 TT genotype was associated with sporadic early onset AD. We now report the study on polymorphism of exon 5 IL-1B in position +3953, the nearest polymorphism to -889 IL-1A. We found that the genotype distribution of IL-1B +3953 varied significantly between patients with early and late onset of AD (P<0.0001). Patients carrying IL-1B +3953 CT or TT genotypes had 4 or 5 years anticipation of AD onset (P=0.0034; odds ratio for early onset, 3.01) and 7 years anticipation if they also carried the IL-1A -889 TT genotype (P<0.0001; odds ratio for early onset, 7.4). These data further support a role for inflammation-related genes in AD or indicate linkage disequilibrium with an unknown chromosome 2 locus.
Sciacca
F L
FL
Department of Neuroscience, Neuroimmunology Unit, AUSL2, via Cusmano 3, Caltanissetta, Italy.
Ferri
C
C
Licastro
F
F
Veglia
F
F
Biunno
I
I
Gavazzi
A
A
Calabrese
E
E
Martinelli Boneschi
F
F
Sorbi
S
S
Mariani
C
C
Franceschi
M
M
Grimaldi
L M E
LM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values
D001057:Apolipoproteins E; D007375:Interleukin-1