Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
J Alzheimers Dis. 2011;23(2):327-33. doi: 10.3233/JAD-2010-101491.
NO synthase, type I (NOS-I) has been suggested to play a role in the etiology of Alzheimer's disease (AD). The gene encoding NOS-I harbors at least nine alternative first exons; in the promoter region of exon 1f, a polymorphic repeat (NOS1 ex1f-VNTR) has been described which influences gene expression and neuronal transcriptome. We have shown that short alleles of this repeat are associated with AD. Here, we sought to further explore this finding by investigating a longitudinal cohort sample from the Vienna-Transdanube-Aging (VITA) study consisting of 606 subjects enrolled at the age of 75 (of these, genotypes were available for 574 subjects) and followed up for 60 months. The ex1f-VNTR risk genotype was associated with AD in the total sample and at the second follow-up. Thus, either long alleles of NOS1 ex1f-VNTR are protective against disease or conversely, short alleles predispose to earlier onset of disease. As demonstrated, ex1f-VNTR interacted with the apolipoprotein E ε4 risk allele (OR in the presence of both risk alleles 3.63; 95% CI: 1.45-9.12). These findings provide further evidence for an association of NOS1 with AD.
I 型一氧化氮合酶 (NOS-I) 被认为在阿尔茨海默病 (AD) 的发病机制中起作用。NOS-I 的编码基因至少含有 9 个替代的第一外显子；在第一外显子 1f 的启动子区域，已经描述了一种多态性重复 (NOS1 ex1f-VNTR)，它影响基因表达和神经元转录组。我们已经表明，这种重复的短等位基因与 AD 有关。在这里，我们通过研究来自维也纳多瑙河衰老研究 (VITA) 的纵向队列样本进一步探索了这一发现，该研究包括 606 名 75 岁时入组的受试者（其中 574 名受试者的基因型可用），并随访 60 个月。在总样本和第二次随访中，ex1f-VNTR 风险基因型与 AD 相关。因此，NOS1 ex1f-VNTR 的长等位基因要么对疾病有保护作用，要么短等位基因易导致疾病更早发作。如前所述，ex1f-VNTR 与载脂蛋白 E ε4 风险等位基因相互作用（存在两个风险等位基因时的 OR 为 3.63；95%CI：1.45-9.12）。这些发现为 NOS1 与 AD 之间的关联提供了进一步的证据。
