Lamb H, Christie J, Singleton A B, Leake A, Perry R H, Ince P G, McKeith I G, Melton L M, Edwardson J A, Morris C M
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne, UK.
Neurology. 1998 Feb;50(2):388-91. doi: 10.1212/wnl.50.2.388.
The possibility of gene interactions in Alzheimer's disease (AD) has been suggested by the finding of an association of the AA genotype of the alpha-1 antichymotrypsin (AACT) gene and the apolipoprotein E (apoE) epsilon 4/4 genotype in AD. We tested this possibility by genotyping a large series of clinically and neuropathologically confirmed cases of AD and a series of cases with dementia with Lewy bodies (DLB) with a matched control group for the AACT locus and apoE. ApoE genotyping showed the established finding of an increased frequency of the apoE epsilon 4 allele in AD and in DLB. The AD and DLB groups differed between each other with a higher epsilon 2 allele frequency and a reduced incidence of the epsilon 4/4 genotype in DLB. Differences in the apoE frequencies may account for some of the differences between the two diseases. No association was found for the AACT A allele in AD or DLB in the groups as a whole or when stratified with respect to apoE, with the exception of a trend showing an increased incidence of the apoE epsilon 4/4 AACT AA genotype combination in AD patients (chi 2 = 3.18, p = 0.07), although in DLB this was not apparent (chi 2 = 0.0, p = 1.0). The AACT A allele is not a major risk factor for late-onset AD or DLB.
α-1抗糜蛋白酶(AACT)基因的AA基因型与载脂蛋白E(apoE)ε4/4基因型在阿尔茨海默病(AD)中的关联这一发现提示了AD中基因相互作用的可能性。我们通过对一系列临床和神经病理学确诊的AD病例以及一系列路易体痴呆(DLB)病例进行基因分型,并与AACT基因座和apoE的匹配对照组进行比较,来检验这种可能性。载脂蛋白E基因分型显示,在AD和DLB中已确定的发现是apoEε4等位基因频率增加。AD组和DLB组彼此不同,DLB中ε2等位基因频率较高,ε4/4基因型的发生率较低。apoE频率的差异可能解释了这两种疾病之间的一些差异。在整个组中或按apoE分层时,未发现AD或DLB中的AACT A等位基因存在关联,但有一个趋势显示AD患者中apoEε4/4 AACT AA基因型组合的发生率增加(χ2 = 3.18,p = 0.07),尽管在DLB中不明显(χ2 = 0.0,p = 1.0)。AACT A等位基因不是晚发性AD或DLB的主要危险因素。