CCR2-64I polymorphism and CCR5Delta32 deletion in patients with Alzheimer's disease.
Monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as their related receptors, have been shown to be involved in Alzheimer's disease (AD) pathogenesis. Genes for their related receptors, CCR2 and CCR5, respectively, are characterized by the presence of two polymorphisms: a conservative change of a valine with an isoleucine at codon 64 of CCR2 (CCR2-64I) and a 32-bp deletion in the coding region of CCR5 (CCR5Delta32), which leads to the expression of a nonfunctional receptor. The distribution of the CCR2-64I and CCR5Delta32 polymorphisms was determined in 290 AD patients and in 222 controls. A decreased frequency and an absence of homozygous for the polymorphism CCR2-64I were found, thus suggesting a protective effect of the mutated allele on the occurrence of AD. However, these findings must be cautiously interpreted as the overall significance was found without adjustment for multiple comparisons and is coming from the complete absence of the genotype 64I/64I in AD patients. Conversely, no different distribution of the CCR5Delta32 deletion in the two populations was shown. Stratifying by the presence of ApoE varepsilon4 allele, gender or age at onset, no differences in either allele frequencies were observed.
Galimberti
Daniela
D
Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122 Milan, Italy.
Fenoglio
Chiara
C
Lovati
Carlo
C
Gatti
Alberto
A
Guidi
Ilaria
I
Venturelli
Eliana
E
Cutter
Gary R
GR
Mariani
Claudio
C
Forloni
Gianluigi
G
Pettenati
Carla
C
Baron
Pierluigi
P
Conti
Giancarlo
G
Bresolin
Nereo
N
Scarpini
Elio
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000096:biosynthesis; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014633:Valine / Q000235:genetics
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C515334:CCR2 protein, human; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D014633:Valine