Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss. Increasing evidence indicates that inflammation in the brain is a powerful factor in AD progression. Epoxyeicosatrienoic acids, the biologically active derivatives of arachidonic acid, synthesized by cytochrome P450 (CYP) epoxygenases, have been proven to have powerful anti-inflammatory effects. The aim of this study was to examine whether polymorphism in CYP2J2, encoding one of the most common CYP epoxygenase isoforms, is associated with late-onset AD (LOAD). This case-control study genotyped 672 representatives of the Chinese Han population, including 321 LOAD patients and 351 healthy controls matched for age and gender, for the functional rs890293 polymorphism within CYP2J2 by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The CYP2J2 rs890293 T allele and GT+TT genotype were significantly associated with an increased risk of LOAD. Further data stratification according to the presence of the apolipoprotein E (APOE) e4 allele confirmed a strong association between CYP2J2 rs890293 and LOAD, and indicated that the involvement of CYP2J2 in LOAD was independent of ApoE-ϵ4. Our study demonstrated that CYP2J2 rs890293 is a possible predisposing genetic factor for progression of LOAD.
Keywords: Alzheimer’s disease; Apolipoprotein E; Cytochrome P450 2J2; Epoxyeicosatrienoic acids; Single nucleotide polymorphism.
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