| 美国研究人员周二表示，已发现有助于确定阿兹海默症（Alzheimer’s disease）或帕金森氏症（Parkinson’s disease）何时会发病的基因。 研究人员表示，对该基因了解得越多，或能帮助医师找出延缓这两种病症的方法。 来自杜克大学医学中心（Duke University Medical Center）和哈佛大学（Harvard University）等机构的研究者发现，这种名为GSTO1的基因与阿兹海默症和帕金森氏症晚年发作有关。 研究者怀疑，该基因会在体内引起发炎反应，杀死引发阿兹海默症和帕金森氏症的脑细胞。 国家老年学研究院（NIA）的莫里森博格拉德（Marcelle Morrison-Bogorad）在声明中说：“这项重要的工作让我们发现了一个值得关注的新基因，该基因可能影响这些晚年型态的退化性神经疾病。”NIA为该研究的资助机构。 “进一步研究该基因、了解其如何作用，将为延缓阿兹海默症或帕金森氏症发作的研究工作开辟一条新途径。” 该研究报告刊登于《人类分子遗传学》（Human Molecular Genetics） Hum. Mol. Genet..2003; 0: 3571-0. Glutathione S-Transferase Omega 1 modifies age-at-onset of Alzheimer Disease and Parkinson Disease. Li YJ, Oliveira SA, Xu P, Martin ER, Stenger JE, Scherzer CR, Hauser MA, Scott WK, Small GW, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Goetz CG, Mastaglia F, Middleton LT, Roses AD, Saunders AM, Schmechel DE, Gullans SR, Haines JL, Gilbert JR, Vance JM, Pericak-Vance MA. Department of Medicine and Center for Human Genetics, Institute for Genome Science and Policy, Duke University Medical Center Box 3445, Durham, North Carolina 27710. We previously reported genetic linkage of loci controlling age-at-onset in Alzheimer disease (AD) and Parkinson disease (PD) to a 15 cM region on chromosome 10q. Given the large number of genes in this initial starting region, we applied our 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 complex 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. |
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