Mellick George D, Maraganore Demetrius M, Silburn Peter A
Department of Neurology, School of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Neurosci Lett. 2005 Feb 28;375(2):112-6. doi: 10.1016/j.neulet.2004.10.078. Epub 2004 Nov 23.
It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic Parkinson's disease (PD). The polymorphic mixed sequence repeat (NACP-Rep1) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for PD with conflicting results. We report genotype and allele distributions at this locus from 369 PD cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR=0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for PD (OR=0.79, 95% CI 0.70-0.89, p=0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association.
目前尚不清楚SNCA（α-突触核蛋白基因）中的基因变异是否会改变散发性帕金森病（PD）的风险。SNCA启动子区域的多态性混合序列重复（NACP-Rep1）先前已被作为PD的潜在易感因素进行研究，但结果相互矛盾。我们报告了369例PD患者和370名欧洲裔澳大利亚对照者在该位点的基因型和等位基因分布，等位基因如前所述被指定为-1、0、+1、+2和+3。与对照组相比，澳大利亚患者中指定为（0）的等位基因频率较低（OR=0.80，95%CI 0.62-1.03）。包括所有先前发表的欧洲祖先Rep1数据的联合分析显示，0等位基因与PD风险降低之间存在高度显著的关联（OR=0.79，95%CI 0.70-0.89，p=0.0001）。现在必须进一步开展研究，以详细检验这种有趣且具有生物学合理性的基因关联。
