TY - JOUR
T1 - CCR2-64I polymorphism and CCR5Δ32 deletion in patients with Alzheimer's disease
AU - Galimberti, Daniela
AU - Fenoglio, Chiara
AU - Lovati, Carlo
AU - Gatti, Alberto
AU - Guidi, Ilaria
AU - Venturelli, Eliana
AU - Cutter, Gary R.
AU - Mariani, Claudio
AU - Forloni, Gianluigi
AU - Pettenati, Carla
AU - Baron, Pierluigi
AU - Conti, Giancarlo
AU - Bresolin, Nereo
AU - Scarpini, Elio
PY - 2004/10/15
Y1 - 2004/10/15
N2 - 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 (CCR5Δ32), which leads to the expression of a nonfunctional receptor. The distribution of the CCR2-64I and CCR5Δ32 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 CCR5Δ32 deletion in the two populations was shown. Stratifying by the presence of ApoE ε4 allele, gender or age at onset, no differences in either allele frequencies were observed.
AB - 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 (CCR5Δ32), which leads to the expression of a nonfunctional receptor. The distribution of the CCR2-64I and CCR5Δ32 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 CCR5Δ32 deletion in the two populations was shown. Stratifying by the presence of ApoE ε4 allele, gender or age at onset, no differences in either allele frequencies were observed.
KW - Alzheimer's disease
KW - Chemokines
KW - Genetics
KW - MCP-1
KW - RANTES
KW - Receptors
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U2 - 10.1016/j.jns.2004.07.005
DO - 10.1016/j.jns.2004.07.005
M3 - Article
C2 - 15465089
AN - SCOPUS:4744369272
VL - 225
SP - 79
EP - 83
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -