Mun Myung-Jin, Kim Jin-Ho, Choi Ji-Young, Kim Min-Seon, Jang Won-Cheoul, Lee Jung Jae, Eun Young Lee, Kwak Shang-June, Kim Ki Woong, Lee Seok Bum
Department of Chemistry, School of Natural Science, Dankook University, Cheonan 330-714, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, South Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, South Korea.
Department of Chemistry, School of Natural Science, Dankook University, Cheonan 330-714, South Korea.
J Neurol Sci. 2016 May 15;364:122-7. doi: 10.1016/j.jns.2016.03.023. Epub 2016 Mar 19.
Sumoylation regulates transcription factor transactivation, protein-protein interactions, and appropriate subcellular localization of certain proteins. Previous studies have shown that sumoylation of amyloid precursor protein (APP) is associated with decreased levels of amyloid beta (Aβ) proteins, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between polymorphisms of the SUMO genes and the risk of AD. Our study subjects consisted of 144 AD patients and 335 healthy controls without dementia. We focused on tagged single nucleotide polymorphisms (tagSNPs) of the SUMO1 and SUMO2 genes. The tagSNPs were amplified by PCR and sequenced. We used binary logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the associations between SUMO gene polymorphisms and the risk of AD. We found that rs12472035 polymorphism of SUMO1 was significantly associated with an increased risk of AD in male group (the CT genotype of rs12472035: adjusted OR=8.737, 95% CI=2.041-37.41, p-value=0.003). In addition, two polymorphisms of SUMO2 were significantly associated with an increased risk of AD in female group (the GA genotype of rs35271045: adjusted OR=2.879, 95% CI=1.399-5.924, p-value=0.004; and the TC genotype of rs9913676: adjusted OR=2.460, 95% CI=1.197-5.057, p-value=0.014). Furthermore, three combinations were associated with an increased risk of AD. Our data suggest that three individual polymorphisms and three combinations may be potential risk factors for AD in Korean population.
SUMO化修饰可调节转录因子的反式激活、蛋白质-蛋白质相互作用以及某些蛋白质在亚细胞中的正确定位。先前的研究表明，淀粉样前体蛋白（APP）的SUMO化修饰与β淀粉样蛋白（Aβ）水平降低有关，这表明SUMO化修饰可能在阿尔茨海默病（AD）的发病机制中起作用。我们研究了SUMO基因多态性与AD风险之间的关联。我们的研究对象包括144例AD患者和335例无痴呆的健康对照。我们重点关注SUMO1和SUMO2基因的标签单核苷酸多态性（tagSNP）。通过聚合酶链反应（PCR）扩增tagSNP并进行测序。我们使用二元逻辑回归计算SUMO基因多态性与AD风险之间关联的比值比（OR）及95%置信区间（CI）。我们发现，SUMO1基因的rs12472035多态性与男性组AD风险增加显著相关（rs12472035的CT基因型：校正OR=8.737，95%CI=2.041-37.41，p值=0.003）。此外，SUMO2基因的两个多态性与女性组AD风险增加显著相关（rs35271045的GA基因型：校正OR=2.879，95%CI=1.399-5.924，p值=0.004；rs9913676的TC基因型：校正OR=2.460，95%CI=1.197-5.057，p值=0.014）。此外，三种组合与AD风险增加相关。我们的数据表明，在韩国人群中，三种个体多态性和三种组合可能是AD的潜在危险因素。
