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J Neurol Sci. 2016 Mar 15;362:27-32. doi: 10.1016/j.jns.2016.01.022. Epub 2016 Jan 15.

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

Author information

1
Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic; Institute of Animal Physiology and Genetics, Academy of Sciences, Veveří 97, 602 00 Brno, Czech Republic. Electronic address: omarsery@sci.muni.cz.
2
Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.
3
Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
4
Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic; Institute of Animal Physiology and Genetics, Academy of Sciences, Veveří 97, 602 00 Brno, Czech Republic.
5
Physiologie de la Nutrition et Toxicologie, UMR U866 INSERM/Université de Bourgogne/Agro-Sup, 6, Boulevard Gabriel, Dijon 21000, France.
6
Discipline Anatomy and Histology and Bosch Institute, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.

Abstract

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.

KEYWORDS:

Alzheimer's disease; Arachidonic acid; Association; Caffeic acid; Curcumin; FLAP; Genetics; Inflammation; Leukotrienes; Polymorphism

PMID:
26944113
DOI:
10.1016/j.jns.2016.01.022
[Indexed for MEDLINE]

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