Study of association between genetic polymorphisms of phospholipase A2 enzymes and Alzheimer's disease

Abstract

Several genes have been related to late-onset Alzheimer's disease (LOAD). Phospholipases A2 (PLA2) influence the processing and secretion of the amyloid precursor protein, which gives rise to the beta-amyloid peptide, the major component of the amyloid plaque in AD. Hence, in the present study, polymorphisms of three genes encoding PLA2 enzymes group (cytosolic PLA2: BanI cPLA2 polymorphism; calcium-independent PLA2: AvrII iPLA2 polymorphism; PAFAH: Val279Phe PAFAH polymorphism) were analysed in a case-control sample using 58 patients with LOAD and 107 matched healthy controls. There was a genotypic association between the BanI cPLA2 polymorphism and LOAD (c 2 =6.25, 2df, p=0.04), however there was no allelic association. There were no associations between AvrII iPLA2 and Val279Phe PAFAH polymorphisms and LOAD. These data suggest that the BanI cPLA2 polymorphism may play a role in the susceptibility for LOAD in our Brazilian sample. Key words: PLA2, dementia, gene, genetics, LOAD.Associação entre polimorfismos das enzimas fosfolipases A2 e doença de Alzheimer resumo Vários genes têm sido investigados como fatores de risco para o desenvolvimento da doença de Alzheimer (DA) de início tardio. As fosfolipases A2 (PLA2) influenciam o processamento e secreção da proteína precursora do amilóide, que dá origem ao peptídeo meta-amilóide, o principal componente da placa amilóide na DA. Assim, no presente estudo, foram analisados três polimorfismos genéticos que codificam enzimas do grupo das PLA2 (PLA2 citosólica: polimorfismo BanI cPLA2; PLA2 cálcio-independente: polimorfismo AvrII iPLA2; PAFAH: polimorfismo Val279Phe PAFAH) em 58 pacientes com DA de início tardio e 107 controles saudáveis pareados. Houve associação genotípica entre o polimorfismo BanI cPLA2 e DA de início tardio (c 2 =6,25, 2df, p=0,04); no entanto não foi observada associação alélica. Não houve associação entre os polimorfismos AvrII iPLA2 e Val279Phe PAFAH com a doença. Tais dados sugerem que o polimorfismo BanI cPLA2 pode estar envolvido como fator de susceptibilidade para DA de início tardio em nossa amostra brasileira. Palavras-chave: PLA2, demência, gene, genética, Alzheimer de início tardio.

Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer’s Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer’s Disease

“…Specific enzyme and gene changes include: 1) Increased levels of several PLC isoforms in AD brain [30–31]; 2) PLD3 gene variants have been reported as a risk factor for AD [32–35] and PLD accumulation occurs in neuritic plaques in AD [36]. Increased gene expression of autotaxin (lysophosphatidate phosphatase) has also been reported for AD frontal cortex [37]; and 3) PLA2 gene variants which have been reported as a risk factor for AD [38–39]. The conjecture that these metabolic pathways may be the main routes to augmented DAG levels in MCI and AD cannot rule out potential contributions by other glycerophospholipids since the size of the pools of these lipids far exceeds that of the DAGs.…”

Dynamics of the Multipathway Regulation of the Vasodilator Bold Effect Induced by a Nerve Impulse: A Kinetic Model of the Neurovascular Coupling Process

“…Particularly characteristic manifestations of molecular polymorphisms of human proteins are related to the functioning of cholinesterase and acylase enzymes. − The structural diversity of the catalytic activity of these enzymes provides a variety of dynamic responses in the same processes. Molecular polymorphisms are the basis of the predisposition to certain diseases. ,− …”

A Dichotomous Role for FABP7 in Sleep and Alzheimer’s Disease Pathogenesis: A Hypothesis

“…The release of AA and DHA are dependent upon the phospholipases (PLAs; Elsherbiny et al, 2013 ) calcium-dependent PLA 2 (cPLA 2 ) and calcium-independent PLA 2 (iPLA 2 ), respectively ( Chakraborti, 2003 ). Interestingly, elevated levels of cPLA 2 immunoreactivity have been found in the astrocytes of post-mortem AD brains ( Stephenson et al, 1996 ), and a genetic polymorphism in cPLA 2 has been associated with late-onset AD ( Cordeiro et al, 2010 ). These findings suggest that cPLA 2 may play a role in the upstream initiation of neuroinflammation in our model.…”