Role of cyclooxygenase-2 and 5-lipoxygenase polymorphisms in Alzheimer's disease in a population from northern Italy: implication for pharmacogenomics.
Alzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by cognitive deficit with progressive worsening of memory. Recent data indicate that neurons, as well as other brain cells, can express enzymes such as cyclooxygenases (COXs) and 5-lipoxygenase (5-LO) which are considered important in inflammatory cells. Moreover, it has been demonstrated that COX-2 and 5-LO enzymes play a considerable role in the pathophysiology of AD. In order to assess the possible role of COX-2 and 5-LO single nucleotide polymorphisms (SNPs) in AD, we examined their distribution in 341 AD patients and 190 controls from Northern Italy. A significant difference was observed in the distribution of the -765G COX-2 and -1708A 5-LO alleles between AD cases and controls (p=0.03 for -765G/C COX-2 SNP; and p=0.007 for -1708G/A 5-LO SNP). Hence, COX-2 -765G and 5-LO -1708A alleles were overrepresented in AD patients and underrepresented in controls. Our data suggest that these alleles of COX-2 and 5-LO could be risk factors for AD. These results seem of some importance for a pharmacogenomic approach.
Listì
Florinda
F
Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Italy.
Caruso
Calogero
C
Lio
Domenico
D
Colonna-Romano
Giuseppina
G
Chiappelli
Martina
M
Licastro
Federico
F
Candore
Giuseppina
G
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044382:Population Groups
D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2