title: Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index.
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.
authors.affiliation: 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.
authors.forename: Omar
authors.initials: O
authors.lastname: Šerý
authors.affiliation: Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.
authors.forename: Lýdia
authors.initials: L
authors.lastname: Hlinecká
authors.affiliation: Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Povová
authors.affiliation: 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.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Bonczek
authors.affiliation: Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Zeman
authors.affiliation: Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Janout
authors.affiliation: Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Ambroz
authors.affiliation: Physiologie de la Nutrition et Toxicologie, UMR U866 INSERM/Université de Bourgogne/Agro-Sup, 6, Boulevard Gabriel, Dijon 21000, France.
authors.forename: Naim A
authors.initials: NA
authors.lastname: Khan
authors.affiliation: Discipline Anatomy and Histology and Bosch Institute, School of Medical Sciences, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Balcar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008019:Life Style; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: D001094:Arachidonate 5-Lipoxygenase; C583212:ALOX5 protein, human
keywords: Alzheimer's disease; Arachidonic acid; Association; Caffeic acid; Curcumin; FLAP; Genetics; Inflammation; Leukotrienes; Polymorphism