No association between the α2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression
No association between the α2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression
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DOI：
10.1007/s007020070052
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发表时间：
2000-01-01
影响因子：
3.3
通讯作者：
Rymo, L
中科院分区：
文献类型：
--
作者：
Blennow, K;Ricksten, A;Rymo, L
在基于家庭的研究中，由α 2-巨球蛋白（A2M）基因（A2M-2）外显子18的5'剪接位点附近的缺失组成的多态性被认为与阿尔茨海默病（AD）有关。我们研究了大量AD患者（n = 449）和年龄匹配对照（n = 349）的A2M-2等位基因和ApoE等位基因。199例（AD 94例，对照107例）经神经病理学确诊。我们发现AD患者的A2M-2基因型或等位基因频率（27.5%和14.6%）与对照组（26.4%和14.9%）相比没有增加。与对照组（29.8%和16.5%）相比，AD患者ApoE epsilon 4基因型或等位基因频率（66.6%和41.2%）显著增加（p < 0.0001），说明我们的样本具有足够的统计能力。A2M-2与ApoE epsilon 4等位基因之间没有关系。在携带A2M-2缺失的病例中，未发现A2M外显子17-18mRNA大小或序列或A2M蛋白大小的变化，这表明A2M内含子缺失没有生物学后果。AD患者脑脊液中A2M蛋白水平未见变化，提示A2M-2等位基因不影响大脑中A2M蛋白的表达。本研究中没有发现A2M-2等位基因与AD之间的关联，也没有发现A2M mRNA或蛋白的异常，这表明A2M-2等位基因与AD无关。
A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha 2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon 4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon 4 allele. No change in A2M exon 17-18mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.