Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
Glutathione S-transferase omega-1 modifies age-at-onset of Alzheimer disease and Parkinson disease
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DOI：
10.1093/hmg/ddg357
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发表时间：
2003-12-15
影响因子：
3.5
通讯作者：
Pericak-Vance, MA
中科院分区：
文献类型：
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作者：
Li, YJ;Oliveira, SA;Pericak-Vance, MA
我们先前报道了控制阿尔茨海默病（AD）和帕金森病（PD）发病年龄的基因座与染色体10 q上15 cM区域的遗传连锁。考虑到这个初始起始区域中的大量基因，我们应用“基因组收敛”的过程来优先考虑并减少候选基因的数量以供进一步分析。作为我们的第二个聚合因子，我们对AD患者和对照组的海马进行了基因表达研究。分析显示，四个基因[硬脂酰辅酶A去饱和酶; NADH-泛醌氧化还原酶1 β亚复合物8;蛋白酶，丝氨酸11;和谷胱甘肽S-转移酶，ω-1（GSTO 1）]在AD和对照之间的表达显著不同，并映射到10 q发病年龄连锁区，第一个收敛因子。使用AD数据集的2814个样本（1773例AD患者）和来自我们PD数据集的1362例样本（635例PD患者），AD和PD发病年龄效应的等位基因关联研究显示，其中3名候选人无关联，但发现GSTO 1（P=0.007）和位于GST 0 1旁边的GST ω类的第二转录成员GST 0 2（P=0.005）。GSTO 1和GSTO 2的功能尚不清楚，但最近的数据表明，GSTO 1可能参与炎症细胞因子白细胞介素-1 β的翻译后修饰。鉴于炎症在这两种神经退行性疾病中的可能作用的报道，这是具有挑衅性的。
We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson's disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied the process of 'genomic convergence' to prioritize and reduce the number of candidate genes for further analysis. As our second convergence factor we performed gene expression studies on hippocampus obtained from AD patients and controls. Analysis revealed that four of the genes [stearoyl-CoA desaturase; NADH-ubiquinone oxidoreductase 1 beta subcomplex 8; protease, serine 11; and glutathione S-transferase, omega-1 (GSTO1)] were significantly different in their expression between AD and controls and mapped to the 10q age-at-onset linkage region, the first convergence factor. Using 2814 samples from our AD dataset (1773 AD patients) and 1362 samples from our PD dataset (635 PD patients), allelic association studies for age-at-onset effects in AD and PD revealed no association for three of the candidates, but a significant association was found for GSTO1 (P=0.007) and a second transcribed member of the GST omega class, GSTO2 (P=0.005), located next to GSTO1. The functions of GSTO1 and GSTO2 are not well understood, but recent data suggest that GSTO1 maybe involved in the post-translational modification of the inflammatory cytokine interleukin-1beta. This is provocative given reports of the possible role of inflammation in these two neurodegenerative disorders.