Šerý Omar, Hlinecká Lýdia, Povová Jana, Bonczek Ondřej, Zeman Tomáš, Janout Vladimír, Ambroz Petr, Khan Naim A, Balcar Vladimir J
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.
Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.
J Neurol Sci. 2016 Mar 15;362:27-32. doi: 10.1016/j.jns.2016.01.022. Epub 2016 Jan 15.
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.
老年痴呆症，尤其是阿尔茨海默病（AD），对全球个人乃至整个社会的寿命和生活质量构成了日益严重的威胁。其风险因素包括遗传和环境（生活方式）因素，并且与心血管疾病（CVD）的类似易感因素存在重叠。通过病例对照基因方法，我们在ALOX5基因中鉴定出一个单核苷酸多态性（SNP，rs10507391），该基因先前与中风风险增加相关，是AD的一个新的遗传风险因素。ALOX5基因编码一种5'-脂氧合酶（5'-LO）激活蛋白（FLAP），它是花生四烯酸/白三烯炎症级联反应的关键组成部分。rs4769874多态性的A等位基因使AD风险增加1.41倍（p<0.0001），而AA基因型则使风险增加1.79倍（p<0.0001）。此外，rs4769874多态性的GG基因型与体重指数（BMI）适度增加相关。我们讨论了将该SNP与AD联系起来的潜在生化机制，并提出了可能的预防性药物治疗方法，其中一些基于常见的天然产物。最后，我们将新发现的AD风险因素置于更广泛的类似CVD风险因素背景中，以更全面地了解可能导致老年心理健康恶化的相互作用的遗传和生活方式习惯。
