Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26944113
DOI
10.1016/j.jns.2016.01.022
PII: S0022-510X(16)30023-5
Knihovny.cz E-resources
- Keywords
- Alzheimer's disease, Arachidonic acid, Association, Caffeic acid, Curcumin, FLAP, Genetics, Inflammation, Leukotrienes, Polymorphism,
- MeSH
- Alzheimer Disease genetics physiopathology psychology MeSH
- Arachidonate 5-Lipoxygenase genetics MeSH
- Genetic Association Studies MeSH
- Genotype MeSH
- Body Mass Index * MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Surveys and Questionnaires MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Body Weight genetics MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- ALOX5 protein, human MeSH Browser
- Arachidonate 5-Lipoxygenase MeSH
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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