Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease
Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease
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DOI：
10.1159/000100021
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发表时间：
2007-01-01
影响因子：
2.4
通讯作者：
Kuo, Yu-Min
中科院分区：
文献类型：
--
作者：
Chuo, Liang-Jen;Sheu, Wayne H. H.;Kuo, Yu-Min
背景资料：位于半胱氨酸蛋白酶抑制剂C（CST 3）外显子1第73位的多态性被认为与阿尔茨海默病（AD）相关，但结果相互矛盾。AD患者CST 3基因型与血浆胱抑素C水平的关系尚不清楚。目的：我们的目标是确定AD和非痴呆对照个体中CST 3多态性与血浆半胱氨酸蛋白酶抑制剂C水平之间的关联。方法：采用PCR和限制性片段长度多态性分析方法检测175例AD患者和461例对照者的CST 3基因型多态性，并采用双抗体夹心ELISA法检测血浆胱抑素C浓度。结果如下：虽然CST 3A等位基因频率在两组之间相似，但CST 3A/A纯合子与晚发性AD显著相关。正如预期的那样，已确定的AD遗传风险因子APOE β 4等位基因在AD队列中的代表性过高。AD患者血浆胱抑素C水平低于对照组。对照组血浆胱抑素C水平与年龄呈正相关，与CST 3A等位基因呈负相关。结论：纯合子CST 3A/A基因型在中国台湾人群中具有AD的危险性。这种关联可能是由于外周循环中半胱氨酸蛋白酶抑制剂C水平降低所致。版权所有（C）2007 S. Karger AG，巴塞尔。
Background: A polymorphism locating at position 73 of cystatin C (CST3) exon 1 was suggested to be associated with Alzheimer disease (AD), but with contradictory results. The relationship between the CST3 genotype and the cystatin C plasma level in AD remains unknown. Objective: We aim to determine the association between CST3 polymorphism and the plasma levels of cystatin C in AD and nondemented control individuals. Method: The polymorphisms of the CST3 genotype were determined using PCR followed by restriction fragment length polymorphism analysis, and the plasma cystatin C concentrations were quantified by sandwich ELISA in 175 AD and 461 control subjects. Results: Although the CST3A allele frequencies were similar between the two groups, the CST3A/A homozygote was significantly associated with late-onset AD. As expected, the established AD genetic risk factor APOE epsilon 4 allele was overrepresented in the AD cohort. The plasma cystatin C levels were lower in the AD patients than in the control group. Furthermore, plasma cystatin C levels were associated positively with age and negatively with CST3A allele in the control group. Conclusion: The homozygous CST3A/A genotype confers a risk for AD in Taiwan Chinese. Such an association may be due to the reduced level of cystatin C in the peripheral circulation. Copyright (C) 2007 S. Karger AG, Basel.