Šerý Omar, Janoutová Jana, Ewerlingová Laura, Hálová Alice, Lochman Jan, Janout Vladimír, 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, Czechia; Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Veveří 97, 602 00, Brno, Czechia.
Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czechia.
Biochimie. 2017 Apr;135:46-53. doi: 10.1016/j.biochi.2017.01.009. Epub 2017 Jan 20.
CD36 gene encodes a membrane glycoprotein (type B scavenger receptor) present on the surface of many types of cells and having multiple cellular functions ranging from angiogenesis to gustatory perception of fatty acids. Using a case control genetic association approach we have analyzed selected single nucleotide polymorphisms (SNP's) in a total of 859 patients with Alzheimer's disease (AD) and controls and have identified the allele A in rs3211892 polymorphism of CD36 gene as significantly increasing the risk of AD. Additionally we have investigated, in the same sample of control subjects and patients, SNP's in ApoE gene and confirmed that the previously identified AD-associated SNP's indeed increased the risk and decreased the age of onset of AD as reported by others earlier. Based on the current knowledge of CD36 biochemistry we propose that the AD risk-imparting variants of CD36 alter cholesterol homeostasis, oxidation stress or induce pathological inflammatory cascades. The SNP rs3211892 has previously been associated with heart disease and other conditions but the present study is the first to identify a significant association between variations in CD36 gene and the risk of Alzheimer's disease.
CD36基因编码一种膜糖蛋白（B型清道夫受体），存在于多种细胞表面，具有从血管生成到脂肪酸味觉感知等多种细胞功能。我们采用病例对照基因关联方法，分析了总共859例阿尔茨海默病（AD）患者和对照者中选定的单核苷酸多态性（SNP），并确定CD36基因rs3211892多态性中的等位基因A显著增加了AD风险。此外，我们在同一组对照受试者和患者样本中研究了载脂蛋白E（ApoE）基因中的SNP，并证实先前确定的与AD相关的SNP确实如其他人先前报道的那样增加了AD风险并降低了发病年龄。基于目前对CD36生物化学的了解，我们提出，赋予AD风险的CD36变体改变了胆固醇稳态、氧化应激或诱导了病理性炎症级联反应。SNP rs3211892先前已与心脏病和其他疾病相关，但本研究首次确定了CD36基因变异与阿尔茨海默病风险之间的显著关联。
