Arachidonate 5-Lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

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Authors

ŠERÝ Omar HLINECKÁ Lýdia POVOVA Jana BONCZEK Ondřej ZEMAN Tomáš JANOUT Vladimír AMBROZ Petr KHAN Naim Akhtar BALCAR Vladimír Josef

Year of publication 2016
Type Article in Periodical
Magazine / Source Journal of the neurological sciences
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1016/j.jns.2016.01.022
Field Neurology, neurosurgery, neurosciences
Keywords Alzheimer's disease; Arachidonic acid; Association; Caffeic acid; Curcumin; FLAP; Genetics; Inflammation; Leukotrienes; Polymorphism
Description Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (life-style) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case-control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5-lipoxygenase (5-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A-allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p = 0.0001), while AA genotype does so 1.79-fold (p = 0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age.
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